1-235775088-TAA-T

Variant names:

• chr1-235775088-TAA-T
• rs557545474
• NM_000081.4:c.5461-4_5461-3delTT

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP6

The NM_000081.4(LYST):​c.5461-4_5461-3delTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000238 in 1,262,848 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in Lovd as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0000068 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000026 (0 hom.)
• Consequence: LYST NM_000081.4 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.40

Genes affected

LYST (HGNC:1968): (lysosomal trafficking regulator) This gene encodes a protein that regulates intracellular protein trafficking in endosomes, and may be involved in pigmentation. Mutations in this gene are associated with Chediak-Higashi syndrome, a lysosomal storage disorder. Alternative splicing results in multiple transcript variants, though the full-length nature of some of these variants has not been determined. [provided by RefSeq, Apr 2013]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 1-235775088-TAA-T is Benign according to our data. Variant chr1-235775088-TAA-T is described in Lovd as [Benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LYST	NM_000081.4	c.5461-4_5461-3delTT		splice_region_variant, intron_variant	Intron 17 of 52	ENST00000389793.7	NP_000072.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LYST	ENST00000389793.7	c.5461-4_5461-3delTT		splice_region_variant, intron_variant	Intron 17 of 52	5	NM_000081.4	ENSP00000374443.2

Frequencies

GnomAD3 genomes AF: 0.00000684 AC: 1 AN: 146224 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000151

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000413 AC: 4 AN: 96916 Hom.: 0 AF XY: 0.0000391 AC XY: 2 AN XY: 51150

Gnomad AFR exome AF: 0.000140

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000100

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000426

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000260 AC: 29 AN: 1116624 Hom.: 0 AF XY: 0.0000234 AC XY: 13 AN XY: 556622

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000300

Gnomad4 FIN exome AF: 0.0000261

Gnomad4 NFE exome AF: 0.0000281

Gnomad4 OTH exome AF: 0.0000438

GnomAD4 genome AF: 0.00000684 AC: 1 AN: 146224 Hom.: 0 Cov.: 32 AF XY: 0.0000141 AC XY: 1 AN XY: 71104

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000151

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs557545474; hg19: chr1-235938388;