rs2433354

Variant names:

• chr15-48122772-C-T
• rs2433354
• NM_205850.3:c.301+736C>T

Variant summary

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

The NM_205850.3(SLC24A5):​c.301+736C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 152,144 control chromosomes in the GnomAD database, including 7,788 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 0.20 (7788 hom., cov: 32)
  • Exomes 𝑓: 0.019 (0 hom.)
• Consequence: SLC24A5 NM_205850.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.505
• Publications: 13 publications found

Genes affected

SLC24A5 (HGNC:20611): (solute carrier family 24 member 5) This gene is a member of the potassium-dependent sodium/calcium exchanger family and encodes an intracellular membrane protein with 2 large hydrophilic loops and 2 sets of multiple transmembrane-spanning segments. Sequence variation in this gene has been associated with differences in skin pigmentation. [provided by RefSeq, Jul 2008]

SLC24A5 Gene-Disease associations (from GenCC):

• oculocutaneous albinism type 6

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.56 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_205850.3. 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
	SLC24A5	NM_205850.3	MANE Select	c.301+736C>T		intron	N/A	NP_995322.1	Q71RS6-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC24A5	ENST00000341459.8	TSL:1 MANE Select	c.301+736C>T		intron	N/A	ENSP00000341550.3	Q71RS6-1
	SLC24A5	ENST00000449382.2	TSL:1	c.121+1607C>T		intron	N/A	ENSP00000389966.2	Q71RS6-2
	SLC24A5	ENST00000482911.2	TSL:2	c.*668C>T		3_prime_UTR	Exon 2 of 2	ENSP00000453395.1	H0YLZ0

Frequencies

GnomAD3 genomes AF: 0.195 AC: 29709 AN: 151974 Hom.: 7757 Cov.: 32

Gnomad AFR AF: 0.566

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.168

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.474

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.00415

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00210

Gnomad OTH AF: 0.155

GnomAD4 exome AF: 0.0192 AC: 1 AN: 52 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 38

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AF: 0.500 AC: 1 AN: 2

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 42

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.196 AC: 29801 AN: 152092 Hom.: 7788 Cov.: 32 AF XY: 0.196 AC XY: 14612 AN XY: 74376

African (AFR) AF: 0.566 AC: 23456 AN: 41412

American (AMR) AF: 0.169 AC: 2575 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3468

East Asian (EAS) AF: 0.474 AC: 2454 AN: 5174

South Asian (SAS) AF: 0.162 AC: 779 AN: 4820

European-Finnish (FIN) AF: 0.00415 AC: 44 AN: 10612

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.00210 AC: 143 AN: 68018

Other (OTH) AF: 0.163 AC: 345 AN: 2112

Alfa AF: 0.101 Hom.: 6457

Bravo AF: 0.226

Asia WGS AF: 0.399 AC: 1380 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.1
DANN	Benign	0.23
PhyloP100		-0.51
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: rs2433354; hg19: chr15-48414969;