2-219628514-C-T

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

1
17

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]

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
SLC4A3NM_005070.4 linkc.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
SLC4A3ENST00000358055.8 linkc.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.:
21
Cov.:
31
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.:
11
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.:
23
Cov.:
31
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.:
21
Cov.:
31
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.:
10
Bravo
AF:
0.0123
ESP6500AA
AF:
0.0345
AC:
152
ESP6500EA
AF:
0.000465
AC:
4
ExAC
AF:
0.00328
AC:
398
Asia WGS
AF:
0.00144
AC:
6
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
T
BayesDel_noAF
Benign
-0.44
CADD
Benign
22
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
D
LIST_S2
Benign
0.72
.;.;T;T
MetaRNN
Benign
0.0023
T;T;T;T
MetaSVM
Benign
-0.97
T
MutationAssessor
Benign
0.34
N;N;N;N
PrimateAI
Benign
0.48
T
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
T
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.

Other links and lift over

dbSNP: rs73072582; hg19: chr2-220493236; API