rs770490496

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr4-682080-C-A
• chr4-682080-C-G
• chr4-682080-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032219.4(SLC49A3):​c.1558G>T​(p.Gly520Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000016 in 1,252,960 control chromosomes in the GnomAD database, with no homozygous occurrence. 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.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000016 (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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10001704).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC49A3	NM_032219.4	c.1558G>T	p.Gly520Cys	missense_variant	Exon 10 of 10	ENST00000322224.9	NP_115595.2
MYL5	NM_002477.2	c.*86C>A		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>T	p.Gly520Cys	missense_variant	Exon 10 of 10	1	NM_032219.4	ENSP00000320234.4
MYL5	ENST00000400159.7	c.*86C>A		downstream_gene_variant		1	NM_002477.2	ENSP00000383023.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000160 AC: 2 AN: 1252960 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 611090

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000174

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Uncertain	0.039	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	11
DANN	Uncertain	0.98
DEOGEN2	Benign	0.021	.;.;T;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.42	T;T;T;T
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.10	T;T;T;T
MetaSVM	Uncertain	0.018	D
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.17	N;N;N;N
REVEL	Uncertain	0.32
Sift	Pathogenic	0.0	D;D;D;D
Polyphen		0.92	P;P;P;P
Vest4		0.18
MutPred		0.16		.;.;Loss of catalytic residue at P517 (P = 0.0775);.;
MVP		0.38
MPC		0.19
ClinPred		0.15	T
GERP RS		-2.9
Varity_R		0.13
gMVP		0.11

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-675869;