rs859098

Variant names:

• chr1-94864816-G-A
• rs859098
• NM_001114106.3:c.1312G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001114106.3(SLC44A3):​c.1312G>A​(p.Val438Ile) variant causes a missense change. The variant allele was found at a frequency of 0.754 in 1,613,502 control chromosomes in the GnomAD database, including 463,126 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.71 (39533 hom., cov: 31)
  • Exomes 𝑓: 0.76 (423593 hom.)
• Consequence: SLC44A3 NM_001114106.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.20
• Publications: 33 publications found

Genes affected

SLC44A3 (HGNC:28689): (solute carrier family 44 member 3) Predicted to enable transmembrane transporter activity. Predicted to be involved in transmembrane transport. Predicted to be located in plasma membrane. Predicted to be active in membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=8.4946697E-7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.96 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC44A3	NM_001114106.3	c.1312G>A	p.Val438Ile	missense_variant	Exon 11 of 15	ENST00000271227.11	NP_001107578.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC44A3	ENST00000271227.11	c.1312G>A	p.Val438Ile	missense_variant	Exon 11 of 15	1	NM_001114106.3	ENSP00000271227.6

Frequencies

GnomAD3 genomes AF: 0.711 AC: 108000 AN: 151946 Hom.: 39514 Cov.: 31

Gnomad AFR AF: 0.536

Gnomad AMI AF: 0.799

Gnomad AMR AF: 0.825

Gnomad ASJ AF: 0.695

Gnomad EAS AF: 0.983

Gnomad SAS AF: 0.780

Gnomad FIN AF: 0.805

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.751

Gnomad OTH AF: 0.733

GnomAD2 exomes AF: 0.781 AC: 196163 AN: 251240 AF XY: 0.779

Gnomad AFR exome AF: 0.537

Gnomad AMR exome AF: 0.882

Gnomad ASJ exome AF: 0.713

Gnomad EAS exome AF: 0.981

Gnomad FIN exome AF: 0.803

Gnomad NFE exome AF: 0.757

Gnomad OTH exome AF: 0.765

GnomAD4 exome AF: 0.759 AC: 1108893 AN: 1461438 Hom.: 423593 Cov.: 44 AF XY: 0.759 AC XY: 551897 AN XY: 727032

African (AFR) AF: 0.531 AC: 17753 AN: 33442

American (AMR) AF: 0.873 AC: 39041 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.712 AC: 18610 AN: 26124

East Asian (EAS) AF: 0.988 AC: 39218 AN: 39696

South Asian (SAS) AF: 0.766 AC: 66063 AN: 86196

European-Finnish (FIN) AF: 0.802 AC: 42837 AN: 53408

Middle Eastern (MID) AF: 0.654 AC: 3775 AN: 5768

European-Non Finnish (NFE) AF: 0.752 AC: 836400 AN: 1111704

Other (OTH) AF: 0.748 AC: 45196 AN: 60384

GnomAD4 genome AF: 0.711 AC: 108075 AN: 152064 Hom.: 39533 Cov.: 31 AF XY: 0.718 AC XY: 53359 AN XY: 74340

African (AFR) AF: 0.536 AC: 22217 AN: 41448

American (AMR) AF: 0.825 AC: 12613 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.695 AC: 2410 AN: 3470

East Asian (EAS) AF: 0.983 AC: 5092 AN: 5180

South Asian (SAS) AF: 0.779 AC: 3741 AN: 4802

European-Finnish (FIN) AF: 0.805 AC: 8509 AN: 10572

Middle Eastern (MID) AF: 0.619 AC: 182 AN: 294

European-Non Finnish (NFE) AF: 0.751 AC: 51038 AN: 67994

Other (OTH) AF: 0.734 AC: 1546 AN: 2106

Alfa AF: 0.745 Hom.: 192336

Bravo AF: 0.707

TwinsUK AF: 0.762 AC: 2824

ALSPAC AF: 0.736 AC: 2837

ESP6500AA AF: 0.548 AC: 2413

ESP6500EA AF: 0.747 AC: 6427

ExAC AF: 0.770 AC: 93497

Asia WGS AF: 0.860 AC: 2989 AN: 3478

EpiCase AF: 0.749

EpiControl AF: 0.752

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.74	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.012	.;T;.;.;.;.
Eigen	Benign	-0.054
Eigen_PC	Benign	-0.029
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.70	T;T;T;T;T;T
MetaRNN	Benign	8.5e-7	T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	.;L;.;.;.;.
PhyloP100		4.2
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.64	N;N;N;N;N;N
REVEL	Benign	0.063
Sift	Benign	0.065	T;T;T;T;T;T
Sift4G	Benign	0.15	T;T;T;T;T;T
Polyphen		0.85	P;B;.;.;.;B
Vest4		0.091
MPC		0.16
ClinPred		0.017	T
GERP RS		5.6
Varity_R		0.099
gMVP		0.095
Mutation Taster		=95/5	polymorphism (auto)

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

Other links and lift over

dbSNP: rs859098; hg19: chr1-95330372; COSMIC: COSV54730929; COSMIC: COSV54730929;