5-33954406-T-C

Variant names:

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 2P and 20B. PM1BP4_StrongBP6_Very_StrongBA1

The NM_001297417.4(SLC45A2):c.661A>G(p.Ser221Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.952 in 1,613,992 control chromosomes in the GnomAD database, including 740,286 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.94 ( 67524 hom., cov: 32)

Exomes 𝑓: 0.95 ( 672762 hom. )

Consequence

SLC45A2
NM_001297417.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -2.36

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 -18 ACMG points.

PM1

In a transmembrane_region Helical; Name=6 (size 20) in uniprot entity S45A2_HUMAN there are 7 pathogenic changes around while only 0 benign (100%) in NM_001297417.4

BP4

Computational evidence support a benign effect (MetaRNN=9.0415114E-7).

BP6

Variant 5-33954406-T-C is Benign according to our data. Variant chr5-33954406-T-C is described in ClinVar as [Benign]. Clinvar id is 197309.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-33954406-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.985 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC45A2	NM_016180.5 link	c.987A>G	p.Thr329Thr	synonymous_variant	Exon 4 of 7	ENST00000296589.9	NP_057264.4	Q9UMX9-1A0A076YGN1A0A076YIB8
SLC45A2	NM_001297417.4 link	c.661A>G	p.Ser221Gly	missense_variant	Exon 3 of 4		NP_001284346.2	Q9UMX9D6RGY6
SLC45A2	NM_001012509.4 link	c.987A>G	p.Thr329Thr	synonymous_variant	Exon 4 of 6		NP_001012527.2	Q9UMX9-4
SLC45A2	XM_047417259.1 link	c.747A>G	p.Thr249Thr	synonymous_variant	Exon 4 of 7		XP_047273215.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLC45A2	ENST00000509381.1 link	c.661A>G	p.Ser221Gly	missense_variant	Exon 3 of 4	1		ENSP00000421100.1	D6RGY6
SLC45A2	ENST00000296589.9 link	c.987A>G	p.Thr329Thr	synonymous_variant	Exon 4 of 7	1	NM_016180.5	ENSP00000296589.4	Q9UMX9-1
SLC45A2	ENST00000382102.7 link	c.987A>G	p.Thr329Thr	synonymous_variant	Exon 4 of 6	1		ENSP00000371534.3	Q9UMX9-4
SLC45A2	ENST00000510600.1 link	c.462A>G	p.Thr154Thr	synonymous_variant	Exon 3 of 5	3		ENSP00000424010.1	D6RBP8

Frequencies

GnomAD3 genomes

AF:

0.938

AC:

142725

AN:

152138

Hom.:

67483

Cov.:

show subpopulations

Gnomad AFR

AF:

0.896

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.916

Gnomad ASJ

AF:

0.982

Gnomad EAS

AF:

0.811

Gnomad SAS

AF:

0.596

Gnomad FIN

AF:

0.997

Gnomad MID

AF:

0.861

Gnomad NFE

AF:

0.991

Gnomad OTH

AF:

0.925

GnomAD3 exomes

AF:

0.899

AC:

225960

AN:

251236

Hom.:

104069

AF XY:

0.889

AC XY:

120635

AN XY:

135758

show subpopulations

Gnomad AFR exome

AF:

0.900

Gnomad AMR exome

AF:

0.841

Gnomad ASJ exome

AF:

0.982

Gnomad EAS exome

AF:

0.813

Gnomad SAS exome

AF:

0.581

Gnomad FIN exome

AF:

0.996

Gnomad NFE exome

AF:

0.989

Gnomad OTH exome

AF:

0.931

GnomAD4 exome

AF:

0.953

AC:

1393719

AN:

1461736

Hom.:

672762

Cov.:

AF XY:

0.943

AC XY:

685779

AN XY:

727164

show subpopulations

Gnomad4 AFR exome

AF:

0.890

Gnomad4 AMR exome

AF:

0.853

Gnomad4 ASJ exome

AF:

0.982

Gnomad4 EAS exome

AF:

0.773

Gnomad4 SAS exome

AF:

0.591

Gnomad4 FIN exome

AF:

0.997

Gnomad4 NFE exome

AF:

0.993

Gnomad4 OTH exome

AF:

0.938

GnomAD4 genome

AF:

0.938

AC:

142831

AN:

152256

Hom.:

67524

Cov.:

AF XY:

0.931

AC XY:

69316

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.895

Gnomad4 AMR

AF:

0.916

Gnomad4 ASJ

AF:

0.982

Gnomad4 EAS

AF:

0.811

Gnomad4 SAS

AF:

0.599

Gnomad4 FIN

AF:

0.997

Gnomad4 NFE

AF:

0.991

Gnomad4 OTH

AF:

0.923

Alfa

AF:

0.974

Hom.:

149172

Bravo

AF:

0.936

TwinsUK

AF:

0.993

AC:

3681

ALSPAC

AF:

0.993

AC:

3826

ESP6500AA

AF:

0.899

AC:

3960

ESP6500EA

AF:

0.990

AC:

8516

ExAC

AF:

0.896

AC:

108827

Asia WGS

AF:

0.683

AC:

2378

AN:

3478

EpiCase

AF:

0.986

EpiControl

AF:

0.986

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

Dec 16, 2014

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Oculocutaneous albinism type 4

Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

Benign:1

Sep 02, 2021

Fulgent Genetics, Fulgent Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.34

CADD

Benign

0.22

DANN

Benign

0.69

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.039

LIST_S2

Benign

0.14

MetaRNN

Benign

9.0e-7

MetaSVM

Benign

-0.94

PROVEAN

Benign

0.060

REVEL

Benign

0.067

Sift

Pathogenic

0.0

Sift4G

Benign

0.49

Polyphen

0.0

Vest4

0.10

ClinPred

0.013

GERP RS

-9.5

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