Variant chr2-161855086-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001178015.2(SLC4A10):c.533C>G(p.Thr178Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000924 in 1,612,106 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 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00010 ( 0 hom. )

Consequence

SLC4A10
NM_001178015.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.91

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:

SLC4A10 (HGNC:):

SLC4A10 links:

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ACMG classification

Classification made for transcript

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=0.3925254).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC4A10	NM_001178015.2 linkuse as main transcript	c.533C>G	p.Thr178Ser	missense_variant	5/27	ENST00000446997.6	NP_001171486.1	Q6U841-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC4A10	ENST00000446997.6 linkuse as main transcript	c.533C>G	p.Thr178Ser	missense_variant	5/27	1	NM_001178015.2	ENSP00000393066.1		Q6U841-1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000201

AC:

AN:

248870

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

134818

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000443

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000101

AC:

147

AN:

1459964

Hom.:

Cov.:

AF XY:

0.0000881

AC XY:

AN XY:

726224

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000131

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152142

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000508

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000596

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

May 27, 2022

The c.533C>G (p.T178S) alteration is located in exon 5 (coding exon 5) of the SLC4A10 gene. This alteration results from a C to G substitution at nucleotide position 533, causing the threonine (T) at amino acid position 178 to be replaced by a serine (S). 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

0.18

BayesDel_addAF

Uncertain

0.049

BayesDel_noAF

Uncertain

-0.040

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.16

.;.;T;T;T

Eigen

Uncertain

0.23

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.88

D;D;D;D;D

M_CAP

Benign

0.022

MetaRNN

Benign

0.39

T;T;T;T;T

MetaSVM

Benign

-0.66

MutationAssessor

Benign

1.2

.;L;.;L;.

MutationTaster

Benign

1.0

D;D;D;D;D;D;D;D

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-2.1

N;N;N;N;N

REVEL

Uncertain

0.31

Sift

Benign

0.34

T;T;T;T;T

Sift4G

Benign

0.27

T;T;T;T;T

Polyphen

0.11, 0.33, 0.056

.;B;.;B;B

Vest4

0.50

MutPred

0.62

.;Loss of sheet (P = 0.1398);Loss of sheet (P = 0.1398);Loss of sheet (P = 0.1398);Loss of sheet (P = 0.1398);

MVP

0.80

MPC

1.0

ClinPred

0.42

GERP RS

5.9

Varity_R

0.25

gMVP

0.36

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

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