rs193922934

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Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001940.4(ATN1):c.1452_1454dup(p.Gln501dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 28)
• Consequence: ATN1 NM_001940.4 inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.13

Genes affected

ATN1 (HGNC:3033): (atrophin 1) Dentatorubral pallidoluysian atrophy (DRPLA) is a rare neurodegenerative disorder characterized by cerebellar ataxia, myoclonic epilepsy, choreoathetosis, and dementia. The disorder is related to the expansion from 7-35 copies to 49-93 copies of a trinucleotide repeat (CAG/CAA) within this gene. The encoded protein includes a serine repeat and a region of alternating acidic and basic amino acids, as well as the variable glutamine repeat. Alternative splicing results in two transcripts variants that encode the same protein. [provided by RefSeq, Jul 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATN1	NM_001940.4	c.1452_1454dup	p.Gln501dup	inframe_insertion	5/10	ENST00000396684.3
ATN1	NM_001007026.2	c.1452_1454dup	p.Gln501dup	inframe_insertion	5/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATN1	ENST00000396684.3	c.1452_1454dup	p.Gln501dup	inframe_insertion	5/10	1	NM_001940.4	P1
ATN1	ENST00000356654.8	c.1452_1454dup	p.Gln501dup	inframe_insertion	5/10	1		P1

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD4 exome Cov.: 44

GnomAD4 genome Cov.: 28

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs193922934; hg19: chr12-7045879;