NM_016180.5:c.1555T>G

Variant names:

• chr5-33944686-A-C
• NM_016180.5:c.1555T>G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_016180.5(SLC45A2):​c.1555T>G​(p.Cys519Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,886 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: SLC45A2 NM_016180.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.09

Genes affected

SLC45A2 (HGNC:16472): (solute carrier family 45 member 2) This gene encodes a transporter protein that mediates melanin synthesis. The protein is expressed in a high percentage of melanoma cell lines. Mutations in this gene are a cause of oculocutaneous albinism type 4, and polymorphisms in this gene are associated with variations in skin and hair color. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.796

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC45A2	NM_016180.5	c.1555T>G	p.Cys519Gly	missense_variant	Exon 7 of 7	ENST00000296589.9	NP_057264.4
SLC45A2	XM_047417259.1	c.1315T>G	p.Cys439Gly	missense_variant	Exon 7 of 7		XP_047273215.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC45A2	ENST00000296589.9	c.1555T>G	p.Cys519Gly	missense_variant	Exon 7 of 7	1	NM_016180.5	ENSP00000296589.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461886 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 727246

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.15
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.75	D
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.86	D
M_CAP	Uncertain	0.16	D
MetaRNN	Pathogenic	0.80	D
MetaSVM	Uncertain	0.077	D
MutationAssessor	Pathogenic	3.0	M
PrimateAI	Benign	0.32	T
PROVEAN	Pathogenic	-4.6	D
REVEL	Pathogenic	0.69
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.038	D
Polyphen		1.0	D
Vest4		0.60
MutPred		0.51		Loss of stability (P = 0.0325);
MVP		0.92
MPC		0.26
ClinPred		0.98	D
GERP RS		4.6
Varity_R		0.64
gMVP		0.72

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: chr5-33944791;