chr5-33946038-A-G

Variant names:

• chr5-33946038-A-G
• rs35406
• ENST00000382102.7:c.*1110T>C

Variant summary

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

The ENST00000382102.7(SLC45A2):​c.*1110T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0273 in 985,366 control chromosomes in the GnomAD database, including 2,107 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 0.066 (1221 hom., cov: 33)
  • Exomes 𝑓: 0.020 (886 hom.)
• Consequence: SLC45A2 ENST00000382102.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.398
• 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: 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.415 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000382102.7. 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.1368+1125T>C		intron	N/A	NP_057264.4
	SLC45A2	NM_001012509.4		c.*1110T>C		3_prime_UTR	Exon 6 of 6	NP_001012527.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC45A2	ENST00000382102.7	TSL:1	c.*1110T>C		3_prime_UTR	Exon 6 of 6	ENSP00000371534.3
	SLC45A2	ENST00000296589.9	TSL:1 MANE Select	c.1368+1125T>C		intron	N/A	ENSP00000296589.4

Frequencies

GnomAD3 genomes AF: 0.0657 AC: 9992 AN: 152166 Hom.: 1212 Cov.: 33

Gnomad AFR AF: 0.0330

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.242

Gnomad ASJ AF: 0.0308

Gnomad EAS AF: 0.429

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.0134

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0185

Gnomad OTH AF: 0.0969

GnomAD4 exome AF: 0.0202 AC: 16845 AN: 833082 Hom.: 886 Cov.: 28 AF XY: 0.0201 AC XY: 7715 AN XY: 384706

African (AFR) AF: 0.0281 AC: 444 AN: 15786

American (AMR) AF: 0.297 AC: 292 AN: 984

Ashkenazi Jewish (ASJ) AF: 0.0320 AC: 165 AN: 5152

East Asian (EAS) AF: 0.426 AC: 1546 AN: 3630

South Asian (SAS) AF: 0.189 AC: 3113 AN: 16456

European-Finnish (FIN) AF: 0.00362 AC: 1 AN: 276

Middle Eastern (MID) AF: 0.159 AC: 257 AN: 1618

European-Non Finnish (NFE) AF: 0.0124 AC: 9463 AN: 761884

Other (OTH) AF: 0.0573 AC: 1564 AN: 27296

GnomAD4 genome AF: 0.0657 AC: 10012 AN: 152284 Hom.: 1221 Cov.: 33 AF XY: 0.0731 AC XY: 5447 AN XY: 74474

African (AFR) AF: 0.0330 AC: 1372 AN: 41570

American (AMR) AF: 0.243 AC: 3718 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0308 AC: 107 AN: 3470

East Asian (EAS) AF: 0.429 AC: 2220 AN: 5170

South Asian (SAS) AF: 0.197 AC: 950 AN: 4820

European-Finnish (FIN) AF: 0.0134 AC: 142 AN: 10618

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.0185 AC: 1256 AN: 68014

Other (OTH) AF: 0.0964 AC: 204 AN: 2116

Alfa AF: 0.0441 Hom.: 714

Bravo AF: 0.0851

Asia WGS AF: 0.244 AC: 847 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.6
DANN	Benign	0.57
PhyloP100		0.40
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: rs35406; hg19: chr5-33946143;