5-33951011-G-T

Variant names:

• chr5-33951011-G-T
• rs35397
• NM_016180.5:c.1156+543C>A

Variant summary

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

The NM_016180.5(SLC45A2):​c.1156+543C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.636 in 152,164 control chromosomes in the GnomAD database, including 40,286 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 0.64 (40286 hom., cov: 31)
• Consequence: SLC45A2 NM_016180.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.581
• Publications: 17 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: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.929 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.1156+543C>A		intron	N/A	NP_057264.4
	SLC45A2	NM_001012509.4		c.1156+543C>A		intron	N/A	NP_001012527.2	Q9UMX9-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC45A2	ENST00000296589.9	TSL:1 MANE Select	c.1156+543C>A		intron	N/A	ENSP00000296589.4	Q9UMX9-1
	SLC45A2	ENST00000382102.7	TSL:1	c.1156+543C>A		intron	N/A	ENSP00000371534.3	Q9UMX9-4
	SLC45A2	ENST00000510600.1	TSL:3	c.631+543C>A		intron	N/A	ENSP00000424010.1	D6RBP8

Frequencies

GnomAD3 genomes AF: 0.637 AC: 96795 AN: 152046 Hom.: 40287 Cov.: 31

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.901

Gnomad AMR AF: 0.545

Gnomad ASJ AF: 0.845

Gnomad EAS AF: 0.0444

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.965

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.935

Gnomad OTH AF: 0.614

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

GnomAD4 genome AF: 0.636 AC: 96791 AN: 152164 Hom.: 40286 Cov.: 31 AF XY: 0.623 AC XY: 46327 AN XY: 74398

African (AFR) AF: 0.198 AC: 8226 AN: 41462

American (AMR) AF: 0.544 AC: 8319 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.845 AC: 2934 AN: 3472

East Asian (EAS) AF: 0.0445 AC: 230 AN: 5174

South Asian (SAS) AF: 0.204 AC: 983 AN: 4818

European-Finnish (FIN) AF: 0.965 AC: 10238 AN: 10612

Middle Eastern (MID) AF: 0.439 AC: 129 AN: 294

European-Non Finnish (NFE) AF: 0.935 AC: 63625 AN: 68016

Other (OTH) AF: 0.608 AC: 1285 AN: 2114

Alfa AF: 0.812 Hom.: 93918

Bravo AF: 0.587

Asia WGS AF: 0.154 AC: 542 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.3
DANN	Benign	0.56
PhyloP100		0.58
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: rs35397; hg19: chr5-33951116;