1-94864816-G-A

Position:

• chr1-94864816-G-A

Variant summary

Our verdict is Benign. Variant got -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. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• 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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
SLC44A3	NM_001114106.3	c.1312G>A	p.Val438Ile	missense_variant	11/15	ENST00000271227.11	NP_001107578.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC44A3	ENST00000271227.11	c.1312G>A	p.Val438Ile	missense_variant	11/15	1	NM_001114106.3	ENSP00000271227	P1

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

GnomAD3 exomes AF: 0.781 AC: 196163 AN: 251240 Hom.: 77859 AF XY: 0.779 AC XY: 105759 AN XY: 135796

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 SAS exome AF: 0.773

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

Gnomad4 AFR exome AF: 0.531

Gnomad4 AMR exome AF: 0.873

Gnomad4 ASJ exome AF: 0.712

Gnomad4 EAS exome AF: 0.988

Gnomad4 SAS exome AF: 0.766

Gnomad4 FIN exome AF: 0.802

Gnomad4 NFE exome AF: 0.752

Gnomad4 OTH exome AF: 0.748

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

Gnomad4 AFR AF: 0.536

Gnomad4 AMR AF: 0.825

Gnomad4 ASJ AF: 0.695

Gnomad4 EAS AF: 0.983

Gnomad4 SAS AF: 0.779

Gnomad4 FIN AF: 0.805

Gnomad4 NFE AF: 0.751

Gnomad4 OTH AF: 0.734

Alfa AF: 0.749 Hom.: 105935

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;.;.;.;.
MutationTaster	Benign	1.0	P;P;P;P;P;P
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

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