4-682080-C-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -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. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G520R) has been classified as Uncertain significance.

• 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
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032219.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC49A3	NM_032219.4	MANE Select	c.1558G>A	p.Gly520Ser	missense	Exon 10 of 10	NP_115595.2
	SLC49A3	NM_001294341.2		c.1561G>A	p.Gly521Ser	missense	Exon 10 of 10	NP_001281270.1	Q6UXD7-1
	SLC49A3	NM_001378061.1		c.1324G>A	p.Gly442Ser	missense	Exon 9 of 9	NP_001364990.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC49A3	ENST00000322224.9	TSL:1 MANE Select	c.1558G>A	p.Gly520Ser	missense	Exon 10 of 10	ENSP00000320234.4	Q6UXD7-2
	SLC49A3	ENST00000404286.6	TSL:1	c.1561G>A	p.Gly521Ser	missense	Exon 10 of 10	ENSP00000384616.2	Q6UXD7-1
	SLC49A3	ENST00000894937.1		c.1441G>A	p.Gly481Ser	missense	Exon 9 of 9	ENSP00000564996.1

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

African (AFR) AF: 0.00 AC: 0 AN: 25596

American (AMR) AF: 0.00 AC: 0 AN: 20946

Ashkenazi Jewish (ASJ) AF: 0.0000577 AC: 1 AN: 17342

East Asian (EAS) AF: 0.00 AC: 0 AN: 31232

South Asian (SAS) AF: 0.00 AC: 0 AN: 57382

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45196

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4716

European-Non Finnish (NFE) AF: 0.00000800 AC: 8 AN: 1000528

Other (OTH) AF: 0.0000200 AC: 1 AN: 50022

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0078	N
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.047	T
MetaSVM	Benign	-0.29	T
PhyloP100		-0.31
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.11	N
REVEL	Benign	0.15
Sift	Pathogenic	0.0	D
Polyphen		0.0010	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
Mutation Taster		=95/5	polymorphism

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: rs770490496; hg19: chr4-675869;