7-107767592-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_000111.3(SLC26A3):c.2258A>G(p.Asn753Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00148 in 1,607,962 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0081 (20 hom., cov: 32)
  • Exomes 𝑓: 0.00079 (11 hom.)
• Consequence: SLC26A3 NM_000111.3 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 2.90

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.005066991).
• BP6: Variant 7-107767592-T-C is Benign according to our data. Variant chr7-107767592-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 358535.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00807 (1229/152284) while in subpopulation AFR AF= 0.0279 (1159/41560). AF 95% confidence interval is 0.0266. There are 20 homozygotes in gnomad4. There are 571 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 20 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC26A3	NM_000111.3	c.2258A>G	p.Asn753Ser	missense_variant	20/21	ENST00000340010.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC26A3	ENST00000340010.10	c.2258A>G	p.Asn753Ser	missense_variant	20/21	1	NM_000111.3	P1
SLC26A3	ENST00000379083.7	c.*1815A>G		3_prime_UTR_variant, NMD_transcript_variant	19/20	2

Frequencies

GnomAD3 genomes AF: 0.00804 AC: 1223 AN: 152166 Hom.: 20 Cov.: 32

Gnomad AFR AF: 0.0278

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00334

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00669

GnomAD3 exomes AF: 0.00199 AC: 500 AN: 250830 Hom.: 4 AF XY: 0.00156 AC XY: 212 AN XY: 135598

Gnomad AFR exome AF: 0.0278

Gnomad AMR exome AF: 0.00107

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000617

Gnomad OTH exome AF: 0.000819

GnomAD4 exome AF: 0.000794 AC: 1156 AN: 1455678 Hom.: 11 Cov.: 29 AF XY: 0.000662 AC XY: 480 AN XY: 724624

Gnomad4 AFR exome AF: 0.0288

Gnomad4 AMR exome AF: 0.00139

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000465

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000352

Gnomad4 OTH exome AF: 0.00150

GnomAD4 genome AF: 0.00807 AC: 1229 AN: 152284 Hom.: 20 Cov.: 32 AF XY: 0.00767 AC XY: 571 AN XY: 74472

Gnomad4 AFR AF: 0.0279

Gnomad4 AMR AF: 0.00334

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000735

Gnomad4 OTH AF: 0.00662

Alfa AF: 0.00160 Hom.: 6

Bravo AF: 0.00951

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0275 AC: 121

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00253 AC: 307

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000119

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	May 14, 2020	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

Congenital secretory diarrhea, chloride type Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.33
Cadd	Benign	18
Dann	Uncertain	0.99
DEOGEN2	Benign	0.094	T
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.067
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.72	T
MetaRNN	Benign	0.0051	T
MetaSVM	Benign	-0.37	T
MutationAssessor	Benign	1.1	L
MutationTaster	Benign	0.75	D;N
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.82	N
REVEL	Uncertain	0.30
Sift	Benign	0.23	T
Sift4G	Benign	0.15	T
Polyphen		0.13	B
Vest4		0.081
MVP		0.82
MPC		0.15
ClinPred		0.044	T
GERP RS		3.5
Varity_R		0.13
gMVP		0.21

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs35342296; hg19: chr7-107408037;