rs26722

Variant summary

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

The NM_016180.5(SLC45A2):c.814G>A(p.Glu272Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0501 in 1,614,096 control chromosomes in the GnomAD database, including 8,984 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.066 ( 1099 hom., cov: 32)

Exomes 𝑓: 0.048 ( 7885 hom. )

Consequence

SLC45A2
NM_016180.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4O:1

Conservation

PhyloP100: 2.05

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=0.002914399).

BP6

Variant 5-33963765-C-T is Benign according to our data. Variant chr5-33963765-C-T is described in ClinVar as [Benign]. Clinvar id is 4504.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-33963765-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.369 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC45A2	NM_016180.5 linkuse as main transcript	c.814G>A	p.Glu272Lys	missense_variant	3/7	ENST00000296589.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC45A2	ENST00000296589.9 linkuse as main transcript	c.814G>A	p.Glu272Lys	missense_variant	3/7	1	NM_016180.5	P1	Q9UMX9-1

Frequencies

GnomAD3 genomes

AF:

0.0661

AC:

10049

AN:

152112

Hom.:

1093

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0468

Gnomad AMI

AF:

0.00987

Gnomad AMR

AF:

0.229

Gnomad ASJ

AF:

0.0343

Gnomad EAS

AF:

0.383

Gnomad SAS

AF:

0.194

Gnomad FIN

AF:

0.0118

Gnomad MID

AF:

0.136

Gnomad NFE

AF:

0.0178

Gnomad OTH

AF:

0.0944

GnomAD3 exomes

AF:

0.118

AC:

29634

AN:

251350

Hom.:

4459

AF XY:

0.113

AC XY:

15312

AN XY:

135854

show subpopulations

Gnomad AFR exome

AF:

0.0489

Gnomad AMR exome

AF:

0.347

Gnomad ASJ exome

AF:

0.0332

Gnomad EAS exome

AF:

0.398

Gnomad SAS exome

AF:

0.197

Gnomad FIN exome

AF:

0.0123

Gnomad NFE exome

AF:

0.0204

Gnomad OTH exome

AF:

0.0967

GnomAD4 exome

AF:

0.0484

AC:

70748

AN:

1461866

Hom.:

7885

Cov.:

AF XY:

0.0521

AC XY:

37888

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.0484

Gnomad4 AMR exome

AF:

0.335

Gnomad4 ASJ exome

AF:

0.0332

Gnomad4 EAS exome

AF:

0.363

Gnomad4 SAS exome

AF:

0.197

Gnomad4 FIN exome

AF:

0.0130

Gnomad4 NFE exome

AF:

0.0145

Gnomad4 OTH exome

AF:

0.0681

GnomAD4 genome

AF:

0.0661

AC:

10065

AN:

152230

Hom.:

1099

Cov.:

AF XY:

0.0730

AC XY:

5433

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.0468

Gnomad4 AMR

AF:

0.229

Gnomad4 ASJ

AF:

0.0343

Gnomad4 EAS

AF:

0.383

Gnomad4 SAS

AF:

0.194

Gnomad4 FIN

AF:

0.0118

Gnomad4 NFE

AF:

0.0178

Gnomad4 OTH

AF:

0.0944

Alfa

AF:

0.0426

Hom.:

1415

Bravo

AF:

0.0842

TwinsUK

AF:

0.0119

AC:

ALSPAC

AF:

0.0176

AC:

ESP6500AA

AF:

0.0497

AC:

219

ESP6500EA

AF:

0.0169

AC:

145

ExAC

AF:

0.107

AC:

12945

Asia WGS

AF:

0.220

AC:

762

AN:

3478

EpiCase

AF:

0.0238

EpiControl

AF:

0.0262

ClinVar

Significance: Benign

Submissions summary: Benign:4Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	This variant is associated with the following publications: (PMID: 15714523, 23071798, 22071478) -

Oculocutaneous albinism type 4

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Mar 06, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

SLC45A2-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 22, 2021

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Skin/hair/eye pigmentation, variation in, 5

Other:1

association, no assertion criteria provided

literature only

OMIM

Feb 13, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.15

Cadd

Benign

Dann

Benign

0.97

DEOGEN2

Benign

0.23

T;.;.

Eigen

Benign

-0.98

Eigen_PC

Benign

-0.86

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.55

T;T;T

MetaRNN

Benign

0.0029

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.2

L;L;.

MutationTaster

Benign

0.13

P;P;P;P;P

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-1.1

N;N;N

REVEL

Benign

0.26

Sift

Benign

0.38

T;T;T

Sift4G

Benign

0.47

T;T;T

Polyphen

0.0030

B;B;.

Vest4

0.13

MPC

0.041

ClinPred

0.0047

GERP RS

2.1

Varity_R

0.037

gMVP

0.39

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