rs1555451498

Variant names:

• chr15-48121986-CTAT-C
• rs1555451498
• NM_205850.3:c.253_255delATT

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PM4_Supporting

The NM_205850.3(SLC24A5):​c.253_255delATT​(p.Ile85del) variant causes a conservative inframe deletion change. The variant allele was found at a frequency of 0.000000684 in 1,461,848 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SLC24A5 NM_205850.3 conservative_inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.18
• Publications: 0 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, Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_205850.3. Strenght limited to Supporting due to length of the change: 1aa.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC24A5	NM_205850.3	c.253_255delATT	p.Ile85del	conservative_inframe_deletion	Exon 2 of 9	ENST00000341459.8	NP_995322.1
SLC24A5	XM_047432394.1	c.253_255delATT	p.Ile85del	conservative_inframe_deletion	Exon 2 of 8		XP_047288350.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC24A5	ENST00000341459.8	c.253_255delATT	p.Ile85del	conservative_inframe_deletion	Exon 2 of 9	1	NM_205850.3	ENSP00000341550.3
SLC24A5	ENST00000449382.2	c.121+823_121+825delATT		intron_variant	Intron 1 of 7	1		ENSP00000389966.2
SLC24A5	ENST00000482911.2	c.253_255delATT	p.Ile85del	conservative_inframe_deletion	Exon 2 of 2	2		ENSP00000453395.1
SLC24A5	ENST00000463289.1	n.13_15delATT		non_coding_transcript_exon_variant	Exon 1 of 5	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461848 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 727238

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111970

Other (OTH) AF: 0.0000166 AC: 1 AN: 60396

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 14, 2016

Genetic Services Laboratory, University of Chicago

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.2

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: rs1555451498; hg19: chr15-48414183;