chr7-107791855-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 1P and 16B. PP3BP6_Very_StrongBS1BS2

The NM_000111.3(SLC26A3):c.357C>A(p.Phe119Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0113 in 1,612,342 control chromosomes in the GnomAD database, including 147 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Benign in ClinVar. Synonymous variant affecting the same amino acid position (i.e. F119F) has been classified as Benign.

Frequency

Genomes: 𝑓 0.0087 ( 19 hom., cov: 32)

Exomes 𝑓: 0.012 ( 128 hom. )

Consequence

SLC26A3
NM_000111.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.455

Publications

7 publications found

Variant links:

Genes affected

SLC26A3 (HGNC:3018): (solute carrier family 26 member 3) The protein encoded by this gene is a transmembrane glycoprotein that transports chloride ions across the cell membrane in exchange for bicarbonate ions. It is localized to the mucosa of the lower intestinal tract, particularly to the apical membrane of columnar epithelium and some goblet cells. The protein is essential for intestinal chloride absorption, and mutations in this gene have been associated with congenital chloride diarrhea. [provided by RefSeq, Oct 2008]

SLC26A3 Gene-Disease associations (from GenCC):

congenital secretory chloride diarrhea 1
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, PanelApp Australia, Ambry Genetics

SLC26A3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -15 ACMG points.

PP3

Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

BP6

Variant 7-107791855-G-T is Benign according to our data. Variant chr7-107791855-G-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 378598.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00873 (1329/152192) while in subpopulation NFE AF = 0.0135 (918/68004). AF 95% confidence interval is 0.0128. There are 19 homozygotes in GnomAd4. There are 657 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 19 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC26A3	NM_000111.3 link	c.357C>A	p.Phe119Leu	missense_variant	Exon 4 of 21	ENST00000340010.10	NP_000102.1	P40879

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLC26A3	ENST00000340010.10 link	c.357C>A	p.Phe119Leu	missense_variant	Exon 4 of 21	1	NM_000111.3	ENSP00000345873.5	P40879
SLC26A3	ENST00000453332.1 link	c.357C>A	p.Phe119Leu	missense_variant	Exon 4 of 4	4		ENSP00000395955.1	C9JFJ2
SLC26A3	ENST00000379083.7 link	n.*148C>A		non_coding_transcript_exon_variant	Exon 4 of 20	2		ENSP00000368375.3	F8WBL6
SLC26A3	ENST00000379083.7 link	n.*148C>A		3_prime_UTR_variant	Exon 4 of 20	2		ENSP00000368375.3	F8WBL6

Frequencies

GnomAD3 genomes

AF:

0.00875

AC:

1330

AN:

152074

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00229

Gnomad AMI

AF:

0.0176

Gnomad AMR

AF:

0.00426

Gnomad ASJ

AF:

0.00576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.0183

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0135

Gnomad OTH

AF:

0.00816

GnomAD2 exomes

AF:

0.00867

AC:

2179

AN:

251348

AF XY:

0.00866

show subpopulations

Gnomad AFR exome

AF:

0.00215

Gnomad AMR exome

AF:

0.00324

Gnomad ASJ exome

AF:

0.00536

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.0164

Gnomad NFE exome

AF:

0.0134

Gnomad OTH exome

AF:

0.00864

GnomAD4 exome

AF:

0.0116

AC:

16870

AN:

1460150

Hom.:

128

Cov.:

AF XY:

0.0111

AC XY:

8069

AN XY:

726474

show subpopulations

African (AFR)

AF:

0.00203

AC:

AN:

33444

American (AMR)

AF:

0.00364

AC:

163

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00570

AC:

149

AN:

26124

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39668

South Asian (SAS)

AF:

0.00157

AC:

135

AN:

86234

European-Finnish (FIN)

AF:

0.0150

AC:

803

AN:

53394

Middle Eastern (MID)

AF:

0.00121

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.0134

AC:

14932

AN:

1110468

Other (OTH)

AF:

0.0101

AC:

612

AN:

60334

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.452

Heterozygous variant carriers

763

1526

2289

3052

3815

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

562

1124

1686

2248

2810

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00873

AC:

1329

AN:

152192

Hom.:

Cov.:

AF XY:

0.00883

AC XY:

657

AN XY:

74412

show subpopulations

African (AFR)

AF:

0.00226

AC:

AN:

41540

American (AMR)

AF:

0.00426

AC:

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.00576

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.000830

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.0183

AC:

194

AN:

10598

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0135

AC:

918

AN:

68004

Other (OTH)

AF:

0.00807

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

118

177

236

295

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000557

Hom.:

Bravo

AF:

0.00733

TwinsUK

AF:

0.0129

AC:

ALSPAC

AF:

0.0148

AC:

ESP6500AA

AF:

0.00340

AC:

ESP6500EA

AF:

0.0136

AC:

117

ExAC

AF:

0.00870

AC:

1056

EpiCase

AF:

0.0112

EpiControl

AF:

0.0111

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 25, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 09, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 29079751) -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Congenital secretory diarrhea, chloride type

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.30

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.45

CADD

Benign

0.045

(source)

DANN

Benign

0.31

DEOGEN2

Uncertain

0.59

D;T

Eigen

Benign

-1.9

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.70

T;T

MetaRNN

Benign

0.029

T;T

MetaSVM

Benign

-0.62

MutationAssessor

Benign

0.43

N;.

PhyloP100

-0.46

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.91

N;N

REVEL

Benign

0.21

Sift

Benign

0.57

T;T

Sift4G

Benign

0.52

T;T

Polyphen

0.0080

B;.

Vest4

0.31

MutPred

0.77

Gain of catalytic residue at F119 (P = 0.0291);Gain of catalytic residue at F119 (P = 0.0291);

MVP

0.57

MPC

0.21

ClinPred

0.00032

GERP RS

-4.0

Varity_R

0.061

gMVP

0.60

Mutation Taster

=97/3

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.67

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.67

Position offset: -25

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over