7-107791855-G-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_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. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). 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

1
17

Clinical Significance

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

Conservation

PhyloP100: -0.455
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6
Variant 7-107791855-G-T is Benign according to our data. Variant chr7-107791855-G-T is described in ClinVar as [Likely_benign]. Clinvar id 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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 19 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLC26A3NM_000111.3 linkc.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 Appris UniProt
SLC26A3ENST00000340010.10 linkc.357C>A p.Phe119Leu missense_variant Exon 4 of 21 1 NM_000111.3 ENSP00000345873.5 P40879
SLC26A3ENST00000453332.1 linkc.357C>A p.Phe119Leu missense_variant Exon 4 of 4 4 ENSP00000395955.1 C9JFJ2
SLC26A3ENST00000379083.7 linkn.*148C>A non_coding_transcript_exon_variant Exon 4 of 20 2 ENSP00000368375.3 F8WBL6
SLC26A3ENST00000379083.7 linkn.*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.:
19
Cov.:
32
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
GnomAD3 exomes
AF:
0.00867
AC:
2179
AN:
251348
Hom.:
12
AF XY:
0.00866
AC XY:
1177
AN XY:
135834
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 SAS exome
AF:
0.00154
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.:
29
AF XY:
0.0111
AC XY:
8069
AN XY:
726474
show subpopulations
Gnomad4 AFR exome
AF:
0.00203
Gnomad4 AMR exome
AF:
0.00364
Gnomad4 ASJ exome
AF:
0.00570
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00157
Gnomad4 FIN exome
AF:
0.0150
Gnomad4 NFE exome
AF:
0.0134
Gnomad4 OTH exome
AF:
0.0101
GnomAD4 genome
AF:
0.00873
AC:
1329
AN:
152192
Hom.:
19
Cov.:
32
AF XY:
0.00883
AC XY:
657
AN XY:
74412
show subpopulations
Gnomad4 AFR
AF:
0.00226
Gnomad4 AMR
AF:
0.00426
Gnomad4 ASJ
AF:
0.00576
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000830
Gnomad4 FIN
AF:
0.0183
Gnomad4 NFE
AF:
0.0135
Gnomad4 OTH
AF:
0.00807
Alfa
AF:
0.000772
Hom.:
18
Bravo
AF:
0.00733
TwinsUK
AF:
0.0129
AC:
48
ALSPAC
AF:
0.0148
AC:
57
ESP6500AA
AF:
0.00340
AC:
15
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

- -

-
Breakthrough Genomics, Breakthrough Genomics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

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) -

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
T
BayesDel_noAF
Benign
-0.45
CADD
Benign
0.045
DANN
Benign
0.31
DEOGEN2
Uncertain
0.59
D;T
Eigen
Benign
-1.9
Eigen_PC
Benign
-1.9
FATHMM_MKL
Benign
0.15
N
LIST_S2
Benign
0.70
T;T
MetaRNN
Benign
0.029
T;T
MetaSVM
Benign
-0.62
T
MutationAssessor
Benign
0.43
N;.
PrimateAI
Benign
0.30
T
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
T
GERP RS
-4.0
Varity_R
0.061
gMVP
0.60

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs73419912; hg19: chr7-107432300; API