5-33964105-T-G

Position:

• chr5-33964105-T-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC45A2	NM_016180.5	c.563-89A>C		intron_variant		ENST00000296589.9	NP_057264.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC45A2	ENST00000296589.9	c.563-89A>C		intron_variant		1	NM_016180.5	ENSP00000296589	P1

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

Gnomad4 AFR exome AF: 0.274

Gnomad4 AMR exome AF: 0.445

Gnomad4 ASJ exome AF: 0.934

Gnomad4 EAS exome AF: 0.107

Gnomad4 SAS exome AF: 0.248

Gnomad4 FIN exome AF: 0.984

Gnomad4 NFE exome AF: 0.973

Gnomad4 OTH exome AF: 0.787

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

Gnomad4 AFR AF: 0.297

Gnomad4 AMR AF: 0.586

Gnomad4 ASJ AF: 0.932

Gnomad4 EAS AF: 0.102

Gnomad4 SAS AF: 0.248

Gnomad4 FIN AF: 0.986

Gnomad4 NFE AF: 0.967

Gnomad4 OTH AF: 0.675

Alfa AF: 0.898 Hom.: 51939

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 15, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	11
DANN	Benign	0.80

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

Publications

LitVar

Other links and lift over

dbSNP: rs183671; hg19: chr5-33964210;