rs41265669

Variant names:

• chr4-71255295-G-A
• rs41265669
• NM_001098484.3:c.149G>A

Your query was ambiguous. Multiple possible variants found:

• chr4-71255295-G-A
• chr4-71255295-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001098484.3(SLC4A4):​c.149G>A​(p.Gly50Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC4A4 NM_001098484.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.35

Genes affected

SLC4A4 (HGNC:11030): (solute carrier family 4 member 4) This gene encodes a sodium bicarbonate cotransporter (NBC) involved in the regulation of bicarbonate secretion and absorption and intracellular pH. Mutations in this gene are associated with proximal renal tubular acidosis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC4A4	NM_001098484.3	c.149G>A	p.Gly50Glu	missense_variant	Exon 3 of 26	ENST00000264485.11	NP_001091954.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC4A4	ENST00000264485.11	c.149G>A	p.Gly50Glu	missense_variant	Exon 3 of 26	1	NM_001098484.3	ENSP00000264485.5

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	Benign	0.28
BayesDel_addAF	Uncertain	0.073	D
BayesDel_noAF	Benign	-0.13
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.58	D;D;.;.;.;.
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.96	.;D;D;D;D;D
M_CAP	Benign	0.071	D
MetaRNN	Uncertain	0.48	T;T;T;T;T;T
MetaSVM	Benign	-0.31	T
MutationAssessor	Benign	0.59	N;N;N;N;.;.
PrimateAI	Uncertain	0.68	T
PROVEAN	Uncertain	-2.5	.;N;N;D;.;.
REVEL	Uncertain	0.31
Sift	Benign	0.24	.;T;T;T;.;.
Sift4G	Uncertain	0.026	.;D;D;D;.;.
Polyphen		0.14	B;B;.;D;.;.
Vest4		0.38, 0.35, 0.38
MutPred		0.28		Gain of glycosylation at T49 (P = 0.0038);Gain of glycosylation at T49 (P = 0.0038);Gain of glycosylation at T49 (P = 0.0038);Gain of glycosylation at T49 (P = 0.0038);.;.;
MVP		0.21
MPC		0.74
ClinPred		0.89	D
GERP RS		5.7
Varity_R		0.41
gMVP		0.28

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: rs41265669; hg19: chr4-72121012; COSMIC: COSV52634028;