Genetic Variant SLC45A2:c.563-8410T>A (chr5-33972426-A-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_016180.5(SLC45A2):c.563-8410T>A variant causes a intron change. The variant allele was found at a frequency of 0.000006 in 333,238 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

SLC45A2
NM_016180.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.82

Publications

5 publications found

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 Gene-Disease associations (from GenCC):

oculocutaneous albinism type 4
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet, G2P, PanelApp Australia

SLC45A2 links:

ENSG00000250914 (HGNC:):

ENSG00000250914 links:

PSMC6P3 (HGNC:34012):

PSMC6P3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016180.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC45A2	NM_016180.5	MANE Select	c.563-8410T>A	intron	N/A	NP_057264.4
SLC45A2	NM_001012509.4		c.563-8410T>A	intron	N/A	NP_001012527.2	Q9UMX9-4
SLC45A2	NM_001297417.4		c.562+9810T>A	intron	N/A	NP_001284346.2	D6RGY6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC45A2	ENST00000296589.9	TSL:1 MANE Select	c.563-8410T>A	intron	N/A	ENSP00000296589.4	Q9UMX9-1
SLC45A2	ENST00000382102.7	TSL:1	c.563-8410T>A	intron	N/A	ENSP00000371534.3	Q9UMX9-4
SLC45A2	ENST00000509381.1	TSL:1	c.562+9810T>A	intron	N/A	ENSP00000421100.1	D6RGY6

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

151946

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.00000552

AC:

AN:

181292

Hom.:

Cov.:

AF XY:

0.00000993

AC XY:

AN XY:

100700

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

4392

American (AMR)

AF:

0.00

AC:

AN:

12202

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3664

East Asian (EAS)

AF:

0.00

AC:

AN:

7420

South Asian (SAS)

AF:

0.00

AC:

AN:

26626

European-Finnish (FIN)

AF:

0.00

AC:

AN:

21594

Middle Eastern (MID)

AF:

0.00

AC:

AN:

532

European-Non Finnish (NFE)

AF:

0.0000103

AC:

AN:

96738

Other (OTH)

AF:

0.00

AC:

AN:

8124

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000658

AC:

AN:

151946

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74206

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41318

American (AMR)

AF:

0.00

AC:

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3462

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10564

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68012

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

3.2

(source)

DANN

Benign

0.73

PhyloP100

5.8

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over