7-107791855-G-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 1P and 16B. PP3 BP6_Very_Strong BS1 BS2

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 (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Benignin 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
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.455

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]

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• PP3: Splicing scoreres supports a deletorius 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 [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 GnomAd at 19 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC26A3	NM_000111.3	c.357C>A	p.Phe119Leu	missense_variant	4/21	ENST00000340010.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC26A3	ENST00000340010.10	c.357C>A	p.Phe119Leu	missense_variant	4/21	1	NM_000111.3	P1
SLC26A3	ENST00000453332.1	c.357C>A	p.Phe119Leu	missense_variant	4/4	4
SLC26A3	ENST00000379083.7	c.*148C>A		3_prime_UTR_variant, NMD_transcript_variant	4/20	2

Frequencies

GnomAD3 genomes AF: 0.00875 AC: 1330 AN: 152074 Hom.: 19 Cov.: 32

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

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

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

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:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Sep 25, 2017	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 09, 2020	This variant is associated with the following publications: (PMID: 29079751) -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

Congenital secretory diarrhea, chloride type Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

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;.
MutationTaster	Benign	0.94	N;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

Other links and lift over

dbSNP: rs73419912; hg19: chr7-107432300;