Variant chr5-33951588-C-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_016180.5(SLC45A2):c.1122G>T(p.Leu374Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,613,938 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Benignin Lovd.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SLC45A2
NM_016180.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.55

Variant links:

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]

SLC45A2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SLC45A2	NM_016180.5 linkuse as main transcript	c.1122G>T	p.Leu374Phe	missense_variant	5/7	ENST00000296589.9	NP_057264.4
SLC45A2	NM_001012509.4 linkuse as main transcript	c.1122G>T	p.Leu374Phe	missense_variant	5/6		NP_001012527.2
SLC45A2	XM_047417259.1 linkuse as main transcript	c.882G>T	p.Leu294Phe	missense_variant	5/7		XP_047273215.1
SLC45A2	NM_001297417.4 linkuse as main transcript	c.*64G>T		3_prime_UTR_variant	4/4		NP_001284346.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC45A2	ENST00000296589.9 linkuse as main transcript	c.1122G>T	p.Leu374Phe	missense_variant	5/7	1	NM_016180.5	ENSP00000296589	P1	Q9UMX9-1
SLC45A2	ENST00000382102.7 linkuse as main transcript	c.1122G>T	p.Leu374Phe	missense_variant	5/6	1		ENSP00000371534		Q9UMX9-4
SLC45A2	ENST00000509381.1 linkuse as main transcript	c.*64G>T		3_prime_UTR_variant	4/4	1		ENSP00000421100
SLC45A2	ENST00000510600.1 linkuse as main transcript	c.597G>T	p.Leu199Phe	missense_variant	4/5	3		ENSP00000424010

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

152080

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461858

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727234

show subpopulations

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000132

AC:

AN:

152080

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74298

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.57

BayesDel_addAF

Pathogenic

0.19

BayesDel_noAF

Uncertain

0.040

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.74

D;.;.

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.71

T;T;T

M_CAP

Uncertain

0.15

MetaRNN

Uncertain

0.71

D;D;D

MetaSVM

Uncertain

0.61

MutationAssessor

Pathogenic

3.0

M;M;.

MutationTaster

Benign

1.0

D;D;D;D;N

PrimateAI

Benign

0.39

PROVEAN

Uncertain

-2.7

D;D;D

REVEL

Pathogenic

0.70

Sift

Uncertain

0.0030

D;D;D

Sift4G

Uncertain

0.0050

D;D;D

Polyphen

0.99

D;D;.

Vest4

0.20

MutPred

0.50

Gain of helix (P = 0.2294);Gain of helix (P = 0.2294);.;

MVP

0.85

MPC

0.27

ClinPred

0.98

GERP RS

4.3

Varity_R

0.39

gMVP

0.90

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over