chr2-161771013-G-A

Position:

chr2-161771013-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4BS1_Supporting

The NM_001178015.2(SLC4A10):c.89G>A(p.Arg30His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000138 in 1,605,968 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00015 ( 0 hom. )

Consequence

SLC4A10
NM_001178015.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.68

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.28198647).

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0000592 (9/151900) while in subpopulation AMR AF= 0.000132 (2/15194). AF 95% confidence interval is 0.0000477. There are 0 homozygotes in gnomad4. There are 6 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC4A10	NM_001178015.2 link	c.89G>A	p.Arg30His	missense_variant	2/27	ENST00000446997.6	NP_001171486.1	Q6U841-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC4A10	ENST00000446997.6 link	c.89G>A	p.Arg30His	missense_variant	2/27	1	NM_001178015.2	ENSP00000393066.1		Q6U841-1

Frequencies

GnomAD3 genomes

AF:

0.0000592

AC:

AN:

151900

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000132

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000627

AC:

AN:

239164

Hom.:

AF XY:

0.0000772

AC XY:

AN XY:

129474

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000149

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000474

Gnomad NFE exome

AF:

0.0000834

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000146

AC:

212

AN:

1454068

Hom.:

Cov.:

AF XY:

0.000151

AC XY:

109

AN XY:

722692

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000136

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000236

Gnomad4 FIN exome

AF:

0.0000189

Gnomad4 NFE exome

AF:

0.000181

Gnomad4 OTH exome

AF:

0.0000333

GnomAD4 genome

AF:

0.0000592

AC:

AN:

151900

Hom.:

Cov.:

AF XY:

0.0000809

AC XY:

AN XY:

74186

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000132

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000566

Hom.:

Bravo

AF:

0.0000718

ExAC

AF:

0.0000415

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 13, 2024

The c.89G>A (p.R30H) alteration is located in exon 2 (coding exon 2) of the SLC4A10 gene. This alteration results from a G to A substitution at nucleotide position 89, causing the arginine (R) at amino acid position 30 to be replaced by a histidine (H). 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

0.14

BayesDel_addAF

Benign

-0.024

BayesDel_noAF

Uncertain

-0.020

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.013

.;.;T;T;T

Eigen

Uncertain

0.58

Eigen_PC

Pathogenic

0.68

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.99

D;D;D;D;D

M_CAP

Benign

0.072

MetaRNN

Benign

0.28

T;T;T;T;T

MetaSVM

Uncertain

-0.27

MutationAssessor

Benign

1.4

.;L;.;L;.

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

-1.1

N;N;N;N;N

REVEL

Uncertain

0.44

Sift

Benign

0.13

T;T;T;T;T

Sift4G

Benign

0.15

T;T;T;T;T

Polyphen

0.98, 0.97, 0.98

.;D;.;D;D

Vest4

0.50

MVP

0.92

MPC

1.3

ClinPred

0.39

GERP RS

5.9

Varity_R

0.16

gMVP

0.49

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over