Variant chr2-74222931-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_133478.3(SLC4A5):c.3268G>C(p.Val1090Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,252 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict 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)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SLC4A5
NM_133478.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.601

Variant links:

Genes affected

SLC4A5 (HGNC:18168): (solute carrier family 4 member 5) This gene encodes a member of the sodium bicarbonate cotransporter (NBC) family, part of the bicarbonate transporter superfamily. Sodium bicarbonate cotransporters are involved in intracellular pH regulation and electroneural or electrogenic sodium bicarbonate transport. This protein is thought to be an integral membrane protein. Multiple transcript variants encoding different isoforms have been found for this gene, but the biological validity of some variants has not been determined. [provided by RefSeq, Jul 2008]

SLC4A5 links:

ENSG00000264324 (HGNC:):

ENSG00000264324 links:

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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=0.12195757).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC4A5	NM_133478.3 link	c.3268G>C	p.Val1090Leu	missense_variant	29/31	ENST00000394019.7	NP_597812.1	Q9BY07-3
SLC4A5	NM_021196.3 link	c.3316G>C	p.Val1106Leu	missense_variant	25/26		NP_067019.3	Q9BY07-1
SLC4A5	NM_001386136.1 link	c.2920G>C	p.Val974Leu	missense_variant	23/25		NP_001373065.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SLC4A5	ENST00000394019.7 link	c.3268G>C	p.Val1090Leu	missense_variant	29/31	5	NM_133478.3	ENSP00000377587.2	Q9BY07-3
ENSG00000264324	ENST00000451608.2 link	n.*3920G>C		non_coding_transcript_exon_variant	35/39	5		ENSP00000416453.2	E7EWF7
ENSG00000264324	ENST00000451608.2 link	n.*3920G>C		3_prime_UTR_variant	35/39	5		ENSP00000416453.2	E7EWF7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000400

AC:

AN:

249710

Hom.:

AF XY:

0.00000741

AC XY:

AN XY:

134926

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:

0.00000885

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460252

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726362

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:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.020

BayesDel_noAF

Benign

-0.27

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.034

.;.;T;.;.;T

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.18

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.79

.;T;T;T;D;.

M_CAP

Benign

0.058

MetaRNN

Benign

0.12

T;T;T;T;T;T

MetaSVM

Benign

-0.68

MutationAssessor

Benign

0.81

.;.;L;.;.;L

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-0.50

N;.;.;N;N;N

REVEL

Benign

0.21

Sift

Benign

0.20

T;.;.;T;D;T

Sift4G

Benign

0.44

T;T;T;T;T;T

Polyphen

0.0040

B;B;B;B;B;B

Vest4

0.18

MutPred

0.17

.;.;Gain of helix (P = 0.062);.;.;Gain of helix (P = 0.062);

MVP

0.44

MPC

0.25

ClinPred

0.17

GERP RS

5.0

Varity_R

0.061

gMVP

0.29

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.14

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over