2-219628514-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 1P and 14B. PP2 BP4_Strong BP6_Moderate BS1 BS2

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 Benign (★).

• Frequency:
  • Genomes: 𝑓 0.010 (21 hom., cov: 31)
  • Exomes 𝑓: 0.0010 (23 hom.)
• Consequence: SLC4A3 NM_005070.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.27

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]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• PP2: Missense variant where missense usually causes diseases, SLC4A3
• 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 [Benign]. Clinvar id is 775826.Status of the report is criteria_provided_single_submitter, 1 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 GnomAd at 1594 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC4A3	NM_005070.4	c.161C>T	p.Pro54Leu	missense_variant	3/23	ENST00000358055.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC4A3	ENST00000358055.8	c.161C>T	p.Pro54Leu	missense_variant	3/23	1	NM_005070.4	P1

Frequencies

GnomAD3 genomes AF: 0.0105 AC: 1594 AN: 152074 Hom.: 21 Cov.: 31

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

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

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

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

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

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
MetaRNN	Benign	0.0023	T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.34	N;N;N;N
MutationTaster	Benign	0.77	N;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

Other links and lift over

dbSNP: rs73072582; hg19: chr2-220493236;