5-33951588-C-G

Position:

chr5-33951588-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000296589.9(SLC45A2):c.1122G>C(p.Leu374Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.824 in 1,613,970 control chromosomes in the GnomAD database, including 626,996 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.64 ( 42245 hom., cov: 32)

Exomes 𝑓: 0.84 ( 584751 hom. )

Consequence

SLC45A2
ENST00000296589.9 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.6710072E-6).

BP6

Variant 5-33951588-C-G is Benign according to our data. Variant chr5-33951588-C-G is described in ClinVar as [Benign]. Clinvar id is 197829.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-33951588-C-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.956 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SLC45A2	NM_016180.5 linkuse as main transcript	c.1122G>C	p.Leu374Phe	missense_variant	5/7	ENST00000296589.9	NP_057264.4
SLC45A2	NM_001012509.4 linkuse as main transcript	c.1122G>C	p.Leu374Phe	missense_variant	5/6		NP_001012527.2
SLC45A2	XM_047417259.1 linkuse as main transcript	c.882G>C	p.Leu294Phe	missense_variant	5/7		XP_047273215.1
SLC45A2	NM_001297417.4 linkuse as main transcript	c.*64G>C		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>C	p.Leu374Phe	missense_variant	5/7	1	NM_016180.5	ENSP00000296589	P1	Q9UMX9-1
SLC45A2	ENST00000382102.7 linkuse as main transcript	c.1122G>C	p.Leu374Phe	missense_variant	5/6	1		ENSP00000371534		Q9UMX9-4
SLC45A2	ENST00000509381.1 linkuse as main transcript	c.*64G>C		3_prime_UTR_variant	4/4	1		ENSP00000421100
SLC45A2	ENST00000510600.1 linkuse as main transcript	c.597G>C	p.Leu199Phe	missense_variant	4/5	3		ENSP00000424010

Frequencies

GnomAD3 genomes

AF:

0.638

AC:

97057

AN:

152040

Hom.:

42249

Cov.:

show subpopulations

Gnomad AFR

AF:

0.163

Gnomad AMI

AF:

0.990

Gnomad AMR

AF:

0.551

Gnomad ASJ

AF:

0.913

Gnomad EAS

AF:

0.00578

Gnomad SAS

AF:

0.0968

Gnomad FIN

AF:

0.984

Gnomad MID

AF:

0.475

Gnomad NFE

AF:

0.962

Gnomad OTH

AF:

0.616

GnomAD3 exomes

AF:

0.645

AC:

162176

AN:

251420

Hom.:

71927

AF XY:

0.645

AC XY:

87606

AN XY:

135888

show subpopulations

Gnomad AFR exome

AF:

0.148

Gnomad AMR exome

AF:

0.381

Gnomad ASJ exome

AF:

0.910

Gnomad EAS exome

AF:

0.00169

Gnomad SAS exome

AF:

0.0970

Gnomad FIN exome

AF:

0.982

Gnomad NFE exome

AF:

0.955

Gnomad OTH exome

AF:

0.737

GnomAD4 exome

AF:

0.844

AC:

1233469

AN:

1461812

Hom.:

584751

Cov.:

AF XY:

0.825

AC XY:

599788

AN XY:

727216

show subpopulations

Gnomad4 AFR exome

AF:

0.130

Gnomad4 AMR exome

AF:

0.402

Gnomad4 ASJ exome

AF:

0.911

Gnomad4 EAS exome

AF:

0.00134

Gnomad4 SAS exome

AF:

0.103

Gnomad4 FIN exome

AF:

0.981

Gnomad4 NFE exome

AF:

0.969

Gnomad4 OTH exome

AF:

0.756

GnomAD4 genome

AF:

0.638

AC:

97039

AN:

152158

Hom.:

42245

Cov.:

AF XY:

0.623

AC XY:

46392

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.163

Gnomad4 AMR

AF:

0.550

Gnomad4 ASJ

AF:

0.913

Gnomad4 EAS

AF:

0.00560

Gnomad4 SAS

AF:

0.0990

Gnomad4 FIN

AF:

0.984

Gnomad4 NFE

AF:

0.962

Gnomad4 OTH

AF:

0.609

Alfa

AF:

0.866

Hom.:

16369

Bravo

AF:

0.589

TwinsUK

AF:

0.971

AC:

3601

ALSPAC

AF:

0.965

AC:

3720

ESP6500AA

AF:

0.185

AC:

814

ESP6500EA

AF:

0.959

AC:

8249

ExAC

AF:

0.640

AC:

77701

Asia WGS

AF:

0.0910

AC:

322

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 25, 2021	This variant is associated with the following publications: (PMID: 15714523, 24616518, 23071798, 19578363, 18650849, 19384953, 18563784, 22464347, 23660638, 19916045, 17999355) -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Dec 09, 2014

- -

Oculocutaneous albinism type 4

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Oculocutaneous albinism type 4;C2673584:SKIN/HAIR/EYE PIGMENTATION 5, BLACK/NONBLACK HAIR

Benign:1

Benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

May 24, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.57

BayesDel_addAF

Benign

-0.23

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

0.93

LIST_S2

Benign

0.71

T;T;T

MetaRNN

Benign

0.0000017

T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Pathogenic

3.0

M;M;.

MutationTaster

Benign

0.0000084

P;P;P;P;P

PrimateAI

Benign

0.39

PROVEAN

Uncertain

-2.7

D;D;D

REVEL

Pathogenic

0.69

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);.;

MPC

0.27

ClinPred

0.029

GERP RS

4.3

Varity_R

0.39

gMVP

0.90

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over