rs588098

Variant names:

• chr1-75251240-C-T
• rs588098
• NM_001130058.2:c.315G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001130058.2(SLC44A5):​c.315G>A​(p.Val105Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.727 in 1,611,776 control chromosomes in the GnomAD database, including 428,590 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.70 (37533 hom., cov: 31)
  • Exomes 𝑓: 0.73 (391057 hom.)
• Consequence: SLC44A5 NM_001130058.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.983
• Publications: 20 publications found

Genes affected

SLC44A5 (HGNC:28524): (solute carrier family 44 member 5) 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP7: Synonymous conserved (PhyloP=0.983 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.911 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC44A5	NM_001130058.2	c.315G>A	p.Val105Val	synonymous_variant	Exon 7 of 24	ENST00000370859.8	NP_001123530.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC44A5	ENST00000370859.8	c.315G>A	p.Val105Val	synonymous_variant	Exon 7 of 24	2	NM_001130058.2	ENSP00000359896.3
SLC44A5	ENST00000370855.5	c.315G>A	p.Val105Val	synonymous_variant	Exon 7 of 24	1		ENSP00000359892.5
SLC44A5	ENST00000469525.1	n.599G>A		non_coding_transcript_exon_variant	Exon 9 of 10	5

Frequencies

GnomAD3 genomes AF: 0.697 AC: 105907 AN: 151872 Hom.: 37532 Cov.: 31

Gnomad AFR AF: 0.570

Gnomad AMI AF: 0.652

Gnomad AMR AF: 0.778

Gnomad ASJ AF: 0.679

Gnomad EAS AF: 0.933

Gnomad SAS AF: 0.774

Gnomad FIN AF: 0.733

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.729

Gnomad OTH AF: 0.705

GnomAD2 exomes AF: 0.746 AC: 187060 AN: 250670 AF XY: 0.744

Gnomad AFR exome AF: 0.562

Gnomad AMR exome AF: 0.837

Gnomad ASJ exome AF: 0.689

Gnomad EAS exome AF: 0.932

Gnomad FIN exome AF: 0.726

Gnomad NFE exome AF: 0.724

Gnomad OTH exome AF: 0.739

GnomAD4 exome AF: 0.730 AC: 1065555 AN: 1459786 Hom.: 391057 Cov.: 42 AF XY: 0.730 AC XY: 530290 AN XY: 726282

African (AFR) AF: 0.563 AC: 18808 AN: 33390

American (AMR) AF: 0.826 AC: 36828 AN: 44596

Ashkenazi Jewish (ASJ) AF: 0.688 AC: 17961 AN: 26098

East Asian (EAS) AF: 0.933 AC: 37019 AN: 39662

South Asian (SAS) AF: 0.745 AC: 64135 AN: 86094

European-Finnish (FIN) AF: 0.726 AC: 38788 AN: 53402

Middle Eastern (MID) AF: 0.646 AC: 3726 AN: 5766

European-Non Finnish (NFE) AF: 0.724 AC: 804383 AN: 1110462

Other (OTH) AF: 0.728 AC: 43907 AN: 60316

GnomAD4 genome AF: 0.697 AC: 105943 AN: 151990 Hom.: 37533 Cov.: 31 AF XY: 0.701 AC XY: 52039 AN XY: 74276

African (AFR) AF: 0.569 AC: 23585 AN: 41422

American (AMR) AF: 0.778 AC: 11889 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.679 AC: 2359 AN: 3472

East Asian (EAS) AF: 0.933 AC: 4814 AN: 5160

South Asian (SAS) AF: 0.771 AC: 3717 AN: 4818

European-Finnish (FIN) AF: 0.733 AC: 7735 AN: 10556

Middle Eastern (MID) AF: 0.643 AC: 189 AN: 294

European-Non Finnish (NFE) AF: 0.729 AC: 49571 AN: 67974

Other (OTH) AF: 0.708 AC: 1493 AN: 2110

Alfa AF: 0.722 Hom.: 179387

Bravo AF: 0.697

Asia WGS AF: 0.826 AC: 2873 AN: 3478

EpiCase AF: 0.729

EpiControl AF: 0.729

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	4.1
DANN	Benign	0.50
PhyloP100		0.98
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=299/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs588098; hg19: chr1-75716925; COSMIC: COSV63758415;