2-219628514-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_005070.4(SLC4A3):c.161C>T(p.Pro54Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00191 in 1,613,652 control chromosomes in the GnomAD database, including 44 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P54S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.010 ( 21 hom., cov: 31)

Exomes 𝑓: 0.0010 ( 23 hom. )

Consequence

SLC4A3
NM_005070.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.27

Variant links:

Genes affected

SLC4A3 (HGNC:11029): (solute carrier family 4 member 3) The protein encoded by this gene is a plasma membrane anion exchange protein. The encoded protein has been found in brain, heart, kidney, small intestine, and lung. [provided by RefSeq, May 2016]

SLC4A3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0022704005).

BP6

Variant 2-219628514-C-T is Benign according to our data. Variant chr2-219628514-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 775826.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0105 (1597/152192) while in subpopulation AFR AF= 0.0366 (1518/41518). AF 95% confidence interval is 0.035. There are 21 homozygotes in gnomad4. There are 734 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1597 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC4A3	NM_005070.4 link	c.161C>T	p.Pro54Leu	missense_variant	Exon 3 of 23	ENST00000358055.8	NP_005061.3	P48751-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC4A3	ENST00000358055.8 link	c.161C>T	p.Pro54Leu	missense_variant	Exon 3 of 23	1	NM_005070.4	ENSP00000350756.3		P48751-1

Frequencies

GnomAD3 genomes

AF:

0.0105

AC:

1594

AN:

152074

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0366

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00412

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00275

AC:

688

AN:

249808

Hom.:

AF XY:

0.00199

AC XY:

269

AN XY:

135356

show subpopulations

Gnomad AFR exome

AF:

0.0375

Gnomad AMR exome

AF:

0.00186

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000436

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000443

Gnomad OTH exome

AF:

0.000986

GnomAD4 exome

AF:

0.00102

AC:

1488

AN:

1461460

Hom.:

Cov.:

AF XY:

0.000820

AC XY:

596

AN XY:

727036

show subpopulations

Gnomad4 AFR exome

AF:

0.0369

Gnomad4 AMR exome

AF:

0.00195

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.0000812

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000126

Gnomad4 OTH exome

AF:

0.00227

GnomAD4 genome

AF:

0.0105

AC:

1597

AN:

152192

Hom.:

Cov.:

AF XY:

0.00987

AC XY:

734

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.0366

Gnomad4 AMR

AF:

0.00412

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00560

Hom.:

Bravo

AF:

0.0123

ESP6500AA

AF:

0.0345

AC:

152

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.00328

AC:

398

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified

Benign:1

Apr 09, 2025

Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.20

T;T;.;T

Eigen

Benign

-0.41

Eigen_PC

Benign

-0.23

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.72

.;.;T;T

MetaRNN

Benign

0.0023

T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.34

N;N;N;N

PrimateAI

Benign

0.48

PROVEAN

Benign

-1.2

N;N;N;N

REVEL

Benign

0.10

Sift

Benign

0.13

T;T;T;T

Sift4G

Benign

0.33

T;T;T;T

Polyphen

0.0

B;B;B;B

Vest4

0.14

MVP

0.64

ClinPred

0.011

GERP RS

2.9

Varity_R

0.056

gMVP

0.30

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