5-33964105-T-G

Variant names:

• chr5-33964105-T-G
• rs183671
• NM_016180.5:c.563-89A>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_016180.5(SLC45A2):​c.563-89A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.841 in 1,360,762 control chromosomes in the GnomAD database, including 532,572 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.69 (44487 hom., cov: 33)
  • Exomes 𝑓: 0.86 (488085 hom.)
• Consequence: SLC45A2 NM_016180.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0810
• Publications: 19 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 5-33964105-T-G is Benign according to our data. Variant chr5-33964105-T-G is described in ClinVar as Benign. ClinVar VariationId is 1233200.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.961 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.563-89A>C		intron	N/A	NP_057264.4
	SLC45A2	NM_001012509.4		c.563-89A>C		intron	N/A	NP_001012527.2
	SLC45A2	NM_001297417.4		c.563-9601A>C		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.563-89A>C		intron	N/A	ENSP00000296589.4
	SLC45A2	ENST00000382102.7	TSL:1	c.563-89A>C		intron	N/A	ENSP00000371534.3
	SLC45A2	ENST00000509381.1	TSL:1	c.563-9601A>C		intron	N/A	ENSP00000421100.1

Frequencies

GnomAD3 genomes AF: 0.690 AC: 104988 AN: 152054 Hom.: 44484 Cov.: 33

Gnomad AFR AF: 0.297

Gnomad AMI AF: 0.990

Gnomad AMR AF: 0.587

Gnomad ASJ AF: 0.932

Gnomad EAS AF: 0.102

Gnomad SAS AF: 0.245

Gnomad FIN AF: 0.986

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.967

Gnomad OTH AF: 0.678

GnomAD4 exome AF: 0.860 AC: 1039223 AN: 1208590 Hom.: 488085 AF XY: 0.842 AC XY: 510700 AN XY: 606246

African (AFR) AF: 0.274 AC: 7683 AN: 28088

American (AMR) AF: 0.445 AC: 15901 AN: 35734

Ashkenazi Jewish (ASJ) AF: 0.934 AC: 22431 AN: 24010

East Asian (EAS) AF: 0.107 AC: 3749 AN: 35182

South Asian (SAS) AF: 0.248 AC: 18801 AN: 75950

European-Finnish (FIN) AF: 0.984 AC: 46814 AN: 47556

Middle Eastern (MID) AF: 0.505 AC: 2659 AN: 5268

European-Non Finnish (NFE) AF: 0.973 AC: 880377 AN: 904966

Other (OTH) AF: 0.787 AC: 40808 AN: 51836

GnomAD4 genome AF: 0.690 AC: 105002 AN: 152172 Hom.: 44487 Cov.: 33 AF XY: 0.677 AC XY: 50373 AN XY: 74396

African (AFR) AF: 0.297 AC: 12306 AN: 41478

American (AMR) AF: 0.586 AC: 8964 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.932 AC: 3235 AN: 3472

East Asian (EAS) AF: 0.102 AC: 528 AN: 5174

South Asian (SAS) AF: 0.248 AC: 1193 AN: 4808

European-Finnish (FIN) AF: 0.986 AC: 10469 AN: 10620

Middle Eastern (MID) AF: 0.602 AC: 177 AN: 294

European-Non Finnish (NFE) AF: 0.967 AC: 65802 AN: 68014

Other (OTH) AF: 0.675 AC: 1425 AN: 2112

Alfa AF: 0.861 Hom.: 66472

Bravo AF: 0.644

Asia WGS AF: 0.249 AC: 872 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

May 15, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	11
DANN	Benign	0.80
PhyloP100		0.081
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: rs183671; hg19: chr5-33964210;