chr1-235663082-T-TAA

Variant names:

• chr1-235663082-T-TAA
• rs36014994
• NM_000081.4:c.11268-6_11268-5dupTT

Variant summary

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

The NM_000081.4(LYST):​c.11268-6_11268-5dupTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.000093 (0 hom.)
• Consequence: LYST NM_000081.4 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.694
• Publications: 6 publications found

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]

LYST Gene-Disease associations (from GenCC):

• Chediak-Higashi syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp, ClinGen, Labcorp Genetics (formerly Invitae), G2P
• attenuated Chédiak-Higashi syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LYST	NM_000081.4	c.11268-6_11268-5dupTT		splice_region_variant, intron_variant	Intron 52 of 52	ENST00000389793.7	NP_000072.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LYST	ENST00000389793.7	c.11268-5_11268-4insTT		splice_region_variant, intron_variant	Intron 52 of 52	5	NM_000081.4	ENSP00000374443.2

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD2 exomes AF: 0.0000245 AC: 4 AN: 163066 AF XY: 0.0000343

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000622

Gnomad NFE exome AF: 0.0000243

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000932 AC: 113 AN: 1212208 Hom.: 0 Cov.: 0 AF XY: 0.0000820 AC XY: 50 AN XY: 609840

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 25918

American (AMR) AF: 0.00 AC: 0 AN: 39786

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22962

East Asian (EAS) AF: 0.0000597 AC: 2 AN: 33480

South Asian (SAS) AF: 0.0000644 AC: 5 AN: 77670

European-Finnish (FIN) AF: 0.0000637 AC: 3 AN: 47102

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4852

European-Non Finnish (NFE) AF: 0.000108 AC: 98 AN: 909204

Other (OTH) AF: 0.0000976 AC: 5 AN: 51234

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.69
Mutation Taster		=97/3	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs36014994; hg19: chr1-235826382;