Variant 2-219629390-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 1P and 8B. PP2BP4_StrongBS2

The NM_005070.4(SLC4A3):c.464C>T(p.Pro155Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000553 in 1,589,922 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P155R) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000040 ( 0 hom. )

Consequence

SLC4A3
NM_005070.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.783

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

PP2

Missense variant where missense usually causes diseases, SLC4A3

BP4

Computational evidence support a benign effect (MetaRNN=0.029349893).

BS2

High AC in GnomAd at 30 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC4A3	NM_005070.4 linkuse as main transcript	c.464C>T	p.Pro155Leu	missense_variant	4/23	ENST00000358055.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC4A3	ENST00000358055.8 linkuse as main transcript	c.464C>T	p.Pro155Leu	missense_variant	4/23	1	NM_005070.4	P1	P48751-1

Frequencies

GnomAD3 genomes

AF:

0.000197

AC:

AN:

152094

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000700

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000765

AC:

AN:

222224

Hom.:

AF XY:

0.0000668

AC XY:

AN XY:

119684

show subpopulations

Gnomad AFR exome

AF:

0.000663

Gnomad AMR exome

AF:

0.0000320

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000170

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000298

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000403

AC:

AN:

1437710

Hom.:

Cov.:

AF XY:

0.0000393

AC XY:

AN XY:

712650

show subpopulations

Gnomad4 AFR exome

AF:

0.000457

Gnomad4 AMR exome

AF:

0.0000238

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.0000244

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000264

Gnomad4 OTH exome

AF:

0.000118

GnomAD4 genome

AF:

0.000197

AC:

AN:

152212

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.000698

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:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000230

ExAC

AF:

0.0000660

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

Jan 16, 2024

The c.464C>T (p.P155L) alteration is located in exon 4 (coding exon 3) of the SLC4A3 gene. This alteration results from a C to T substitution at nucleotide position 464, causing the proline (P) at amino acid position 155 to be replaced by a leucine (L). 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

0.063

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.42

Cadd

Benign

Dann

Uncertain

0.98

DEOGEN2

Benign

0.27

T;T;.;T

Eigen

Benign

-0.60

Eigen_PC

Benign

-0.51

FATHMM_MKL

Benign

0.43

M_CAP

Benign

0.0090

MetaRNN

Benign

0.029

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

L;L;L;L

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-1.8

N;N;N;N

REVEL

Benign

0.13

Sift

Uncertain

0.0040

D;D;D;D

Sift4G

Benign

0.079

T;T;T;T

Polyphen

0.0010

B;B;B;B

Vest4

0.22

MutPred

0.16

Loss of glycosylation at P155 (P = 0.0557);Loss of glycosylation at P155 (P = 0.0557);Loss of glycosylation at P155 (P = 0.0557);Loss of glycosylation at P155 (P = 0.0557);

MVP

0.34

ClinPred

0.032

GERP RS

3.2

Varity_R

0.066

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