2-161804490-G-C

Position:

• chr2-161804490-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001178015.2(SLC4A10):​c.172G>C​(p.Gly58Arg) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC4A10 NM_001178015.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.31

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]

SLC4A10 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33065993).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC4A10	NM_001178015.2	c.172G>C	p.Gly58Arg	missense_variant	3/27	ENST00000446997.6	NP_001171486.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC4A10	ENST00000446997.6	c.172G>C	p.Gly58Arg	missense_variant	3/27	1	NM_001178015.2	ENSP00000393066.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 14, 2024

The c.172G>C (p.G58R) alteration is located in exon 3 (coding exon 3) of the SLC4A10 gene. This alteration results from a G to C substitution at nucleotide position 172, causing the glycine (G) at amino acid position 58 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.046	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0025	.;.;T;T;T
Eigen	Uncertain	0.19
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.90	D;D;D;D;D
M_CAP	Uncertain	0.16	D
MetaRNN	Benign	0.33	T;T;T;T;T
MetaSVM	Uncertain	-0.18	T
MutationAssessor	Benign	-0.34	.;N;.;N;.
MutationTaster	Benign	1.0	D;D;D;D;D;D;D;D
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	0.23	N;N;N;N;N
REVEL	Uncertain	0.33
Sift	Benign	0.66	T;T;T;T;T
Sift4G	Benign	0.54	T;T;T;T;T
Polyphen		0.95, 0.017, 0.011	.;P;.;B;B
Vest4		0.49
MutPred		0.32		.;Loss of methylation at R59 (P = 0.0575);Loss of methylation at R59 (P = 0.0575);Loss of methylation at R59 (P = 0.0575);Loss of methylation at R59 (P = 0.0575);
MVP		0.83
MPC		1.1
ClinPred		0.94	D
GERP RS		5.4
Varity_R		0.22
gMVP		0.46

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: chr2-162661000;