chr5-33972426-A-C

Variant names:

• chr5-33972426-A-C
• rs35415
• NM_016180.5:c.563-8410T>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.563-8410T>G variant causes a intron change. The variant allele was found at a frequency of 0.54 in 332,740 control chromosomes in the GnomAD database, including 51,206 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 0.55 (23646 hom., cov: 32)
  • Exomes 𝑓: 0.53 (27560 hom.)
• Consequence: SLC45A2 NM_016180.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.82
• Publications: 5 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet, G2P, PanelApp Australia

ENSG00000250914 (HGNC:):

PSMC6P3 (HGNC:34012):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.591 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.563-8410T>G		intron	N/A	NP_057264.4
	SLC45A2	NM_001012509.4		c.563-8410T>G		intron	N/A	NP_001012527.2	Q9UMX9-4
	SLC45A2	NM_001297417.4		c.562+9810T>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.563-8410T>G		intron	N/A	ENSP00000296589.4	Q9UMX9-1
	SLC45A2	ENST00000382102.7	TSL:1	c.563-8410T>G		intron	N/A	ENSP00000371534.3	Q9UMX9-4
	SLC45A2	ENST00000509381.1	TSL:1	c.562+9810T>G		intron	N/A	ENSP00000421100.1	D6RGY6

Frequencies

GnomAD3 genomes AF: 0.551 AC: 83725 AN: 151870 Hom.: 23642 Cov.: 32

Gnomad AFR AF: 0.529

Gnomad AMI AF: 0.586

Gnomad AMR AF: 0.477

Gnomad ASJ AF: 0.583

Gnomad EAS AF: 0.447

Gnomad SAS AF: 0.210

Gnomad FIN AF: 0.662

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.596

Gnomad OTH AF: 0.519

GnomAD4 exome AF: 0.531 AC: 95980 AN: 180750 Hom.: 27560 Cov.: 0 AF XY: 0.507 AC XY: 50880 AN XY: 100400

African (AFR) AF: 0.543 AC: 2370 AN: 4368

American (AMR) AF: 0.426 AC: 5177 AN: 12140

Ashkenazi Jewish (ASJ) AF: 0.559 AC: 2041 AN: 3654

East Asian (EAS) AF: 0.459 AC: 3398 AN: 7400

South Asian (SAS) AF: 0.222 AC: 5904 AN: 26576

European-Finnish (FIN) AF: 0.663 AC: 14280 AN: 21530

Middle Eastern (MID) AF: 0.438 AC: 233 AN: 532

European-Non Finnish (NFE) AF: 0.601 AC: 57971 AN: 96442

Other (OTH) AF: 0.568 AC: 4606 AN: 8108

GnomAD4 genome AF: 0.551 AC: 83749 AN: 151990 Hom.: 23646 Cov.: 32 AF XY: 0.546 AC XY: 40568 AN XY: 74302

African (AFR) AF: 0.529 AC: 21896 AN: 41424

American (AMR) AF: 0.476 AC: 7269 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.583 AC: 2017 AN: 3462

East Asian (EAS) AF: 0.447 AC: 2307 AN: 5162

South Asian (SAS) AF: 0.210 AC: 1009 AN: 4816

European-Finnish (FIN) AF: 0.662 AC: 6992 AN: 10560

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.596 AC: 40536 AN: 67972

Other (OTH) AF: 0.515 AC: 1086 AN: 2110

Alfa AF: 0.575 Hom.: 25469

Bravo AF: 0.543

Asia WGS AF: 0.322 AC: 1125 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	3.3
DANN	Benign	0.66
PhyloP100		5.8
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: rs35415; hg19: chr5-33972531; COSMIC: COSV56875780;