rs35391

Variant names:

• chr5-33955568-T-C
• rs35391
• NM_016180.5:c.889-1064A>G

Variant summary

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

The NM_016180.5(SLC45A2):​c.889-1064A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.806 in 152,128 control chromosomes in the GnomAD database, including 52,530 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 (52530 hom., cov: 31)
• Consequence: SLC45A2 NM_016180.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.04
• Publications: 44 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: PanelApp Australia, Ambry Genetics, G2P, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.968 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC45A2	NM_016180.5	MANE Select	c.889-1064A>G		intron	N/A	NP_057264.4
	SLC45A2	NM_001012509.4		c.889-1064A>G		intron	N/A	NP_001012527.2	Q9UMX9-4
	SLC45A2	NM_001297417.4		c.563-1064A>G		intron	N/A	NP_001284346.2	D6RGY6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC45A2	ENST00000296589.9	TSL:1 MANE Select	c.889-1064A>G		intron	N/A	ENSP00000296589.4	Q9UMX9-1
	SLC45A2	ENST00000382102.7	TSL:1	c.889-1064A>G		intron	N/A	ENSP00000371534.3	Q9UMX9-4
	SLC45A2	ENST00000509381.1	TSL:1	c.563-1064A>G		intron	N/A	ENSP00000421100.1	D6RGY6

Frequencies

GnomAD3 genomes AF: 0.806 AC: 122492 AN: 152010 Hom.: 52522 Cov.: 31

Gnomad AFR AF: 0.622

Gnomad AMI AF: 0.990

Gnomad AMR AF: 0.656

Gnomad ASJ AF: 0.951

Gnomad EAS AF: 0.391

Gnomad SAS AF: 0.397

Gnomad FIN AF: 0.985

Gnomad MID AF: 0.734

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: 0.806 AC: 122542 AN: 152128 Hom.: 52530 Cov.: 31 AF XY: 0.793 AC XY: 58986 AN XY: 74382

African (AFR) AF: 0.622 AC: 25766 AN: 41438

American (AMR) AF: 0.655 AC: 9996 AN: 15262

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

East Asian (EAS) AF: 0.391 AC: 2022 AN: 5168

South Asian (SAS) AF: 0.400 AC: 1928 AN: 4816

European-Finnish (FIN) AF: 0.985 AC: 10470 AN: 10626

Middle Eastern (MID) AF: 0.738 AC: 217 AN: 294

European-Non Finnish (NFE) AF: 0.975 AC: 66302 AN: 68028

Other (OTH) AF: 0.775 AC: 1637 AN: 2112

Alfa AF: 0.904 Hom.: 267561

Bravo AF: 0.774

Asia WGS AF: 0.422 AC: 1472 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.079
DANN	Benign	0.47
PhyloP100		-2.0
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs35391;

hg19: chr5-33955673;