Variant chr7-151064944-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP5BP4

The NM_003040.4(SLC4A2):c.556G>A(p.Ala186Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,118 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. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SLC4A2
NM_003040.4 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 1.10

Variant links:

Genes affected

SLC4A2 (HGNC:11028): (solute carrier family 4 member 2) This gene encodes a member of the anion exchanger family of membrane transport proteins. The encoded protein regulates intracellular pH, biliary bicarbonate secretion, and chloride uptake. Reduced expression of this gene may be associated with primary biliary cirrhosis (PBC) in human patients, while differential expression of this gene may be associated with malignant hepatocellular carcinoma, colon and gastric cancers. [provided by RefSeq, Nov 2016]

SLC4A2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 7-151064944-G-A is Pathogenic according to our data. Variant chr7-151064944-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 2500827.Status of the report is no_assertion_criteria_provided, 0 stars.

BP4

Computational evidence support a benign effect (MetaRNN=0.20087719). . Strength limited to SUPPORTING due to the PP5.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SLC4A2	NM_003040.4 linkuse as main transcript	c.556G>A	p.Ala186Thr	missense_variant	5/23	ENST00000413384.7	NP_003031.3
SLC4A2	NM_001199692.3 linkuse as main transcript	c.556G>A	p.Ala186Thr	missense_variant	5/23		NP_001186621.1
SLC4A2	NM_001199693.1 linkuse as main transcript	c.529G>A	p.Ala177Thr	missense_variant	4/22		NP_001186622.1
SLC4A2	NM_001199694.2 linkuse as main transcript	c.514G>A	p.Ala172Thr	missense_variant	4/22		NP_001186623.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC4A2	ENST00000413384.7 linkuse as main transcript	c.556G>A	p.Ala186Thr	missense_variant	5/23	1	NM_003040.4	ENSP00000405600	P1	P04920-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461118

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726898

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.:

Bravo

AF:

0.00000378

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Osteopetrosis, autosomal recessive 9

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Oct 02, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.0062

BayesDel_noAF

Benign

-0.25

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.059

T;T;.;.

Eigen

Uncertain

0.26

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Benign

0.69

LIST_S2

Benign

0.79

.;T;T;T

M_CAP

Benign

0.032

MetaRNN

Benign

0.20

T;T;T;T

MetaSVM

Benign

-0.54

MutationAssessor

Benign

1.4

L;L;.;.

MutationTaster

Benign

0.74

N;N;N;N;N

PrimateAI

Benign

0.44

PROVEAN

Benign

-0.48

N;N;N;N

REVEL

Benign

0.22

Sift

Benign

0.28

T;T;T;T

Sift4G

Benign

0.43

T;T;T;T

Polyphen

0.95

P;P;.;D

Vest4

0.24

MutPred

0.15

Gain of phosphorylation at A186 (P = 0.0082);Gain of phosphorylation at A186 (P = 0.0082);.;.;

MVP

0.72

MPC

0.55

ClinPred

0.41

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.068

gMVP

0.20

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

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