rs386833444

Positions:

• chr7-107783296-C-A
• chr7-107783296-C-G
• chr7-107783296-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PM5 PP3_Moderate

The NM_000111.3(SLC26A3):​c.1028G>T​(p.Cys343Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C343Y) has been classified as Likely pathogenic.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC26A3 NM_000111.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.01

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_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM5: Other missense variant is known to change same aminoacid residue: Variant chr7-107783296-C-T is described in Lovd as [Likely_pathogenic].
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.926

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC26A3	NM_000111.3	c.1028G>T	p.Cys343Phe	missense_variant	9/21	ENST00000340010.10	NP_000102.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC26A3	ENST00000340010.10	c.1028G>T	p.Cys343Phe	missense_variant	9/21	1	NM_000111.3	ENSP00000345873	P1
SLC26A3	ENST00000468551.1	n.306G>T		non_coding_transcript_exon_variant	3/5	2
SLC26A3	ENST00000379083.7	c.*819G>T		3_prime_UTR_variant, NMD_transcript_variant	9/20	2		ENSP00000368375

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.84
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.60	D
Eigen	Benign	0.058
Eigen_PC	Benign	0.061
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.67	T
M_CAP	Uncertain	0.091	D
MetaRNN	Pathogenic	0.93	D
MetaSVM	Uncertain	0.21	D
MutationAssessor	Benign	1.8	L
MutationTaster	Benign	0.96	N;N
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-2.4	N
REVEL	Uncertain	0.52
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
Polyphen		0.46	P
Vest4		0.61
MutPred		0.81		Gain of helix (P = 0.2294);
MVP		0.90
MPC		0.62
ClinPred		0.94	D
GERP RS		4.3
Varity_R		0.63
gMVP		0.93

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-107423741;