rs35390

Variant names:

• chr5-33955221-C-A
• rs35390
• NM_016180.5:c.889-717G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016180.5(SLC45A2):​c.889-717G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.805 in 152,086 control chromosomes in the GnomAD database, including 52,511 homozygotes. 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 0.81 (52511 hom., cov: 31)
• Consequence: SLC45A2 NM_016180.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.931
• Publications: 22 publications found

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: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.968 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC45A2	NM_016180.5	c.889-717G>T		intron_variant	Intron 3 of 6	ENST00000296589.9	NP_057264.4
SLC45A2	NM_001012509.4	c.889-717G>T		intron_variant	Intron 3 of 5		NP_001012527.2
SLC45A2	NM_001297417.4	c.563-717G>T		intron_variant	Intron 2 of 3		NP_001284346.2
SLC45A2	XM_047417259.1	c.649-717G>T		intron_variant	Intron 3 of 6		XP_047273215.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC45A2	ENST00000296589.9	c.889-717G>T		intron_variant	Intron 3 of 6	1	NM_016180.5	ENSP00000296589.4
SLC45A2	ENST00000382102.7	c.889-717G>T		intron_variant	Intron 3 of 5	1		ENSP00000371534.3
SLC45A2	ENST00000509381.1	c.563-717G>T		intron_variant	Intron 2 of 3	1		ENSP00000421100.1
SLC45A2	ENST00000510600.1	c.364-717G>T		intron_variant	Intron 2 of 4	3		ENSP00000424010.1

Frequencies

GnomAD3 genomes AF: 0.806 AC: 122455 AN: 151968 Hom.: 52503 Cov.: 31

Gnomad AFR AF: 0.622

Gnomad AMI AF: 0.990

Gnomad AMR AF: 0.655

Gnomad ASJ AF: 0.951

Gnomad EAS AF: 0.392

Gnomad SAS AF: 0.397

Gnomad FIN AF: 0.985

Gnomad MID AF: 0.732

Gnomad NFE AF: 0.975

Gnomad OTH AF: 0.778

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.805 AC: 122505 AN: 152086 Hom.: 52511 Cov.: 31 AF XY: 0.793 AC XY: 58955 AN XY: 74354

African (AFR) AF: 0.622 AC: 25753 AN: 41408

American (AMR) AF: 0.655 AC: 10000 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.951 AC: 3301 AN: 3472

East Asian (EAS) AF: 0.392 AC: 2020 AN: 5154

South Asian (SAS) AF: 0.400 AC: 1930 AN: 4826

European-Finnish (FIN) AF: 0.985 AC: 10453 AN: 10608

Middle Eastern (MID) AF: 0.736 AC: 215 AN: 292

European-Non Finnish (NFE) AF: 0.975 AC: 66293 AN: 68022

Other (OTH) AF: 0.774 AC: 1637 AN: 2114

Alfa AF: 0.892 Hom.: 115763

Bravo AF: 0.774

Asia WGS AF: 0.421 AC: 1471 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	11
DANN	Benign	0.72
PhyloP100		0.93
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs35390; hg19: chr5-33955326;