4-682080-C-T

Variant names:

• chr4-682080-C-T
• rs770490496
• NM_032219.4:c.1558G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_032219.4(SLC49A3):​c.1558G>A​(p.Gly520Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000798 in 1,252,960 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000080 (0 hom.)
• Consequence: SLC49A3 NM_032219.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.312

Genes affected

SLC49A3 (HGNC:26177): (solute carrier family 49 member 3) Predicted to enable transmembrane transporter activity. Predicted to be involved in transmembrane transport. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

MYL5 (HGNC:7586): (myosin light chain 5) This gene encodes one of the myosin light chains, a component of the hexameric ATPase cellular motor protein myosin. Myosin is composed of two heavy chains, two nonphosphorylatable alkali light chains, and two phosphorylatable regulatory light chains. This gene product, one of the regulatory light chains, is expressed in fetal muscle and in adult retina, cerebellum, and basal ganglia. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.046682686).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC49A3	NM_032219.4	c.1558G>A	p.Gly520Ser	missense_variant	Exon 10 of 10	ENST00000322224.9	NP_115595.2
MYL5	NM_002477.2	c.*86C>T		downstream_gene_variant		ENST00000400159.7	NP_002468.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC49A3	ENST00000322224.9	c.1558G>A	p.Gly520Ser	missense_variant	Exon 10 of 10	1	NM_032219.4	ENSP00000320234.4
MYL5	ENST00000400159.7	c.*86C>T		downstream_gene_variant		1	NM_002477.2	ENSP00000383023.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000798 AC: 10 AN: 1252960 Hom.: 0 Cov.: 31 AF XY: 0.00000818 AC XY: 5 AN XY: 611090

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0000577

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000800

Gnomad4 OTH exome AF: 0.0000200

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.080	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	1.2
DANN	Benign	0.81
DEOGEN2	Benign	0.018	.;.;T;T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0078	N
LIST_S2	Benign	0.50	T;T;T;T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.047	T;T;T;T
MetaSVM	Benign	-0.29	T
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.11	N;N;N;N
REVEL	Benign	0.15
Sift	Pathogenic	0.0	D;D;D;D
Polyphen		0.0010	B;B;B;B
Vest4		0.11
MutPred		0.15		.;.;Gain of glycosylation at G521 (P = 0.0029);.;
MVP		0.24
MPC		0.085
ClinPred		0.032	T
GERP RS		-2.9
Varity_R		0.076
gMVP		0.12

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: rs770490496; hg19: chr4-675869;