rs749911186

Variant names:

• chr12-51475175-C-G
• rs749911186
• NM_001039960.3:c.2141C>G

Your query was ambiguous. Multiple possible variants found:

• chr12-51475175-C-G
• chr12-51475175-C-T

Variant summary

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

The NM_001039960.3(SLC4A8):​c.2141C>G​(p.Thr714Arg) 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 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)
• Consequence: SLC4A8 NM_001039960.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.983

Genes affected

SLC4A8 (HGNC:11034): (solute carrier family 4 member 8) The protein encoded by this gene is a membrane protein that functions to transport sodium and bicarbonate ions across the cell membrane. The encoded protein is important for pH regulation in neurons. The activity of this protein can be inhibited by 4,4'-Di-isothiocyanatostilbene-2,2'-disulfonic acid (DIDS). Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2012]

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
SLC4A8	NM_001039960.3	c.2141C>G	p.Thr714Arg	missense_variant	Exon 16 of 25	ENST00000453097.7	NP_001035049.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC4A8	ENST00000453097.7	c.2141C>G	p.Thr714Arg	missense_variant	Exon 16 of 25	1	NM_001039960.3	ENSP00000405812.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000247 AC: 3

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Uncertain	0.071	D
BayesDel_noAF	Benign	-0.14
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.18	.;T;.
Eigen	Benign	0.030
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.79	T;T;T
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.31	T;T;T
MetaSVM	Benign	-0.44	T
MutationAssessor	Benign	0.81	.;L;.
PrimateAI	Benign	0.40	T
PROVEAN	Benign	0.46	.;N;N
REVEL	Uncertain	0.33
Sift	Benign	0.26	.;T;T
Sift4G	Benign	0.23	T;T;T
Polyphen		0.30	.;B;.
Vest4		0.36
MutPred		0.44		.;Gain of MoRF binding (P = 0.0201);.;
MVP		0.12
MPC		0.99
ClinPred		0.67	D
GERP RS		5.6
Varity_R		0.15
gMVP		0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.27		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.27		Position offset: 31

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

Publications

LitVar

Other links and lift over

dbSNP: rs749911186; hg19: chr12-51868959;