chr7-107765871-A-G

Variant names:

• chr7-107765871-A-G
• rs1793904957
• NM_000111.3:c.2279T>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000111.3(SLC26A3):​c.2279T>C​(p.Val760Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,459,230 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SLC26A3 NM_000111.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.492

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0218364).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC26A3	NM_000111.3	c.2279T>C	p.Val760Ala	missense_variant	Exon 21 of 21	ENST00000340010.10	NP_000102.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC26A3	ENST00000340010.10	c.2279T>C	p.Val760Ala	missense_variant	Exon 21 of 21	1	NM_000111.3	ENSP00000345873.5
SLC26A3	ENST00000379083.7	n.*1836T>C		non_coding_transcript_exon_variant	Exon 20 of 20	2		ENSP00000368375.3
SLC26A3	ENST00000379083.7	n.*1836T>C		3_prime_UTR_variant	Exon 20 of 20	2		ENSP00000368375.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1459230 Hom.: 0 Cov.: 28 AF XY: 0.00000275 AC XY: 2 AN XY: 726112

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	0.038
DANN	Benign	0.32
DEOGEN2	Benign	0.082	T
Eigen	Benign	-2.2
Eigen_PC	Benign	-2.3
FATHMM_MKL	Benign	0.024	N
LIST_S2	Benign	0.12	T
M_CAP	Uncertain	0.098	D
MetaRNN	Benign	0.022	T
MetaSVM	Benign	-0.49	T
MutationAssessor	Benign	0.55	N
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-0.63	N
REVEL	Benign	0.28
Sift	Benign	0.42	T
Sift4G	Benign	0.48	T
Polyphen		0.0010	B
Vest4		0.032
MutPred		0.17		Gain of relative solvent accessibility (P = 0.0023);
MVP		0.46
MPC		0.21
ClinPred		0.73	D
GERP RS		-10
Varity_R		0.025
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: rs1793904957; hg19: chr7-107406316;