1-235759040-AT-GA

Variant names:

• chr1-235759040-AT-GA
• NM_000081.4:c.6812_6813delATinsTC
• LYST p.Asp2271Val

Variant summary

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

The NM_000081.4(LYST):​c.6812_6813delATinsTC​(p.Asp2271Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D2271G) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LYST NM_000081.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.20
• Publications: 0 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: G2P, Labcorp Genetics (formerly Invitae), Orphanet, ClinGen, Genomics England PanelApp
• attenuated Chédiak-Higashi syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000081.4. 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
	LYST	NM_000081.4	MANE Select	c.6812_6813delATinsTC	p.Asp2271Val	missense	N/A	NP_000072.2	Q99698-1
	LYST	NM_001301365.1		c.6812_6813delATinsTC	p.Asp2271Val	missense	N/A	NP_001288294.1	Q99698-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LYST	ENST00000389793.7	TSL:5 MANE Select	c.6812_6813delATinsTC	p.Asp2271Val	missense	N/A	ENSP00000374443.2	Q99698-1
	LYST	ENST00000697241.1		c.1244_1245delATinsTC	p.Asp415Val	missense	N/A	ENSP00000513206.1	A0A8V8TM69
	LYST	ENST00000461526.2	TSL:3	n.1487_1488delATinsTC		non_coding_transcript_exon	Exon 7 of 28	ENSP00000513165.1	A0A8V8TL52

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.2

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr1-235922340;