5-33969523-T-C

Variant names:

• chr5-33969523-T-C
• rs35414
• NM_016180.5:c.563-5507A>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.563-5507A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.45 in 152,084 control chromosomes in the GnomAD database, including 20,401 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 0.45 (20401 hom., cov: 31)
• Consequence: SLC45A2 NM_016180.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.46
• Publications: 13 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 = 0.648 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC45A2	NM_016180.5	MANE Select	c.563-5507A>G		intron	N/A	NP_057264.4
	SLC45A2	NM_001012509.4		c.563-5507A>G		intron	N/A	NP_001012527.2
	SLC45A2	NM_001297417.4		c.562+12713A>G		intron	N/A	NP_001284346.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC45A2	ENST00000296589.9	TSL:1 MANE Select	c.563-5507A>G		intron	N/A	ENSP00000296589.4
	SLC45A2	ENST00000382102.7	TSL:1	c.563-5507A>G		intron	N/A	ENSP00000371534.3
	SLC45A2	ENST00000509381.1	TSL:1	c.562+12713A>G		intron	N/A	ENSP00000421100.1

Frequencies

GnomAD3 genomes AF: 0.450 AC: 68435 AN: 151966 Hom.: 20405 Cov.: 31

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.612

Gnomad AMR AF: 0.405

Gnomad ASJ AF: 0.637

Gnomad EAS AF: 0.176

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.754

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.653

Gnomad OTH AF: 0.429

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

GnomAD4 genome AF: 0.450 AC: 68417 AN: 152084 Hom.: 20401 Cov.: 31 AF XY: 0.445 AC XY: 33117 AN XY: 74340

African (AFR) AF: 0.114 AC: 4716 AN: 41506

American (AMR) AF: 0.404 AC: 6178 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.637 AC: 2208 AN: 3466

East Asian (EAS) AF: 0.176 AC: 908 AN: 5170

South Asian (SAS) AF: 0.102 AC: 493 AN: 4820

European-Finnish (FIN) AF: 0.754 AC: 7972 AN: 10566

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.653 AC: 44400 AN: 67968

Other (OTH) AF: 0.425 AC: 896 AN: 2110

Alfa AF: 0.574 Hom.: 37106

Bravo AF: 0.415

Asia WGS AF: 0.140 AC: 491 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	12
DANN	Benign	0.74
PhyloP100		2.5
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: rs35414; hg19: chr5-33969628;