2-161839848-A-T

Position:

• chr2-161839848-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2 PP2 BP4_Moderate

The NM_001178015.2(SLC4A10):​c.337A>T​(p.Ile113Phe) variant causes a missense change. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I113V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC4A10 NM_001178015.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.81

Genes affected

SLC4A10 (HGNC:13811): (solute carrier family 4 member 10) This gene belongs to a small family of sodium-coupled bicarbonate transporters (NCBTs) that regulate the intracellular pH of neurons, the secretion of bicarbonate ions across the choroid plexus, and the pH of the brain extracellular fluid. The protein encoded by this gene was initially identified as a sodium-driven chloride bicarbonate exchanger (NCBE) though there is now evidence that its sodium/bicarbonate cotransport activity is independent of any chloride ion countertransport under physiological conditions. This gene is now classified as a member A10 of the SLC4 family of transmembrane solute carriers. Alternative splicing results in multiple transcript variants encoding distinct isoforms.[provided by RefSeq, May 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, SLC4A10
• BP4: Computational evidence support a benign effect (MetaRNN=0.2622093).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC4A10	NM_001178015.2	c.337A>T	p.Ile113Phe	missense_variant	4/27	ENST00000446997.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC4A10	ENST00000446997.6	c.337A>T	p.Ile113Phe	missense_variant	4/27	1	NM_001178015.2	P4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Uncertain	0.049	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	24
DANN	Benign	0.95
Eigen	Benign	-0.018
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.95	D;D;D;D;D
M_CAP	Benign	0.056	D
MetaRNN	Benign	0.26	T;T;T;T;T
MetaSVM	Benign	-0.48	T
MutationTaster	Benign	1.0	D;D;D;D;D;D;D;D
PrimateAI	Pathogenic	0.83	D
PROVEAN	Uncertain	-2.8	D;D;D;D;D
REVEL	Uncertain	0.32
Sift	Benign	0.048	D;D;D;T;D
Sift4G	Benign	0.14	T;T;T;T;T
Polyphen		0.018, 0.0090, 0.0030	.;B;.;B;B
Vest4		0.45
MutPred		0.34		.;Loss of helix (P = 0.0376);Loss of helix (P = 0.0376);Loss of helix (P = 0.0376);Loss of helix (P = 0.0376);
MVP		0.80
MPC		0.83
ClinPred		0.97	D
GERP RS		4.4
Varity_R		0.34
gMVP		0.30

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs929159822; hg19: chr2-162696358;