5-33944624-T-G

Variant names:

• chr5-33944624-T-G
• rs45552240
• NM_016180.5:c.*24A>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_016180.5(SLC45A2):​c.*24A>C variant causes a splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00324 in 1,611,258 control chromosomes in the GnomAD database, including 106 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0020 (7 hom., cov: 33)
  • Exomes 𝑓: 0.0034 (99 hom.)
• Consequence: SLC45A2 NM_016180.5 splice_region
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.151
• Publications: 2 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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 5-33944624-T-G is Benign according to our data. Variant chr5-33944624-T-G is described in ClinVar as Likely_benign. ClinVar VariationId is 906956.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00204 (311/152274) while in subpopulation SAS AF = 0.0345 (166/4816). AF 95% confidence interval is 0.0302. There are 7 homozygotes in GnomAd4. There are 186 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 7 AR gene

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.*24A>C		splice_region	Exon 7 of 7	NP_057264.4
	SLC45A2	NM_016180.5	MANE Select	c.*24A>C		3_prime_UTR	Exon 7 of 7	NP_057264.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC45A2	ENST00000296589.9	TSL:1 MANE Select	c.*24A>C		splice_region	Exon 7 of 7	ENSP00000296589.4	Q9UMX9-1
	SLC45A2	ENST00000296589.9	TSL:1 MANE Select	c.*24A>C		3_prime_UTR	Exon 7 of 7	ENSP00000296589.4	Q9UMX9-1

Frequencies

GnomAD3 genomes AF: 0.00204 AC: 311 AN: 152156 Hom.: 7 Cov.: 33

Gnomad AFR AF: 0.000386

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00137

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0346

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.00137

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.00571 AC: 1417 AN: 248050 AF XY: 0.00773

Gnomad AFR exome AF: 0.000251

Gnomad AMR exome AF: 0.00102

Gnomad ASJ exome AF: 0.000600

Gnomad EAS exome AF: 0.000164

Gnomad FIN exome AF: 0.0000465

Gnomad NFE exome AF: 0.00177

Gnomad OTH exome AF: 0.00610

GnomAD4 exome AF: 0.00336 AC: 4903 AN: 1458984 Hom.: 99 Cov.: 31 AF XY: 0.00452 AC XY: 3278 AN XY: 725850

African (AFR) AF: 0.000539 AC: 18 AN: 33424

American (AMR) AF: 0.00132 AC: 59 AN: 44618

Ashkenazi Jewish (ASJ) AF: 0.000997 AC: 26 AN: 26076

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39688

South Asian (SAS) AF: 0.0365 AC: 3133 AN: 85912

European-Finnish (FIN) AF: 0.000319 AC: 17 AN: 53352

Middle Eastern (MID) AF: 0.0158 AC: 91 AN: 5766

European-Non Finnish (NFE) AF: 0.00117 AC: 1304 AN: 1109856

Other (OTH) AF: 0.00418 AC: 252 AN: 60292

GnomAD4 genome AF: 0.00204 AC: 311 AN: 152274 Hom.: 7 Cov.: 33 AF XY: 0.00250 AC XY: 186 AN XY: 74466

African (AFR) AF: 0.000385 AC: 16 AN: 41556

American (AMR) AF: 0.00137 AC: 21 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.0345 AC: 166 AN: 4816

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10620

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.00137 AC: 93 AN: 68016

Other (OTH) AF: 0.00237 AC: 5 AN: 2112

Alfa AF: 0.00185 Hom.: 1

Bravo AF: 0.00114

Asia WGS AF: 0.0120 AC: 43 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	Oculocutaneous albinism type 4 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.3
DANN	Benign	0.69
PhyloP100		0.15
Mutation Taster		=100/0	polymorphism

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: rs45552240; hg19: chr5-33944729; COSMIC: COSV56871857; COSMIC: COSV56871857;