22-45795354-G-GATTCTATTCTATTCT

Position:

• chr22-45795354-G-GATTCTATTCTATTCT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The ENST00000252934.10(ATXN10):​c.1174-11549_1174-11535dup variant causes a 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: 𝑓 0.0077 (20 hom., cov: 0)
• Consequence: ATXN10 ENST00000252934.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.237

Genes affected

ATXN10 (HGNC:10549): (ataxin 10) This gene encodes a protein that may function in neuron survival, neuron differentiation, and neuritogenesis. These roles may be carried out via activation of the mitogen-activated protein kinase cascade. Expansion of an ATTCT repeat from 9-32 copies to 800-4500 copies in an intronic region of this locus has been associated with spinocerebellar ataxia, type 10. Alternatively spliced transcript variants have been described.[provided by RefSeq, Jul 2016]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00768 (973/126632) while in subpopulation EAS AF= 0.0462 (186/4028). AF 95% confidence interval is 0.0408. There are 20 homozygotes in gnomad4. There are 461 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 973 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATXN10	NM_013236.4	c.1174-11549_1174-11535dup		intron_variant		ENST00000252934.10	NP_037368.1
ATXN10	NM_001167621.2	c.982-11549_982-11535dup		intron_variant			NP_001161093.1
ATXN10	XM_047441314.1	c.1174-11549_1174-11535dup		intron_variant			XP_047297270.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATXN10	ENST00000252934.10	c.1174-11549_1174-11535dup		intron_variant		1	NM_013236.4	ENSP00000252934	P1

Frequencies

GnomAD3 genomes AF: 0.00766 AC: 969 AN: 126526 Hom.: 20 Cov.: 0

Gnomad AFR AF: 0.00608

Gnomad AMI AF: 0.00735

Gnomad AMR AF: 0.00770

Gnomad ASJ AF: 0.00553

Gnomad EAS AF: 0.0464

Gnomad SAS AF: 0.00910

Gnomad FIN AF: 0.00252

Gnomad MID AF: 0.00345

Gnomad NFE AF: 0.00661

Gnomad OTH AF: 0.00882

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

GnomAD4 genome AF: 0.00768 AC: 973 AN: 126632 Hom.: 20 Cov.: 0 AF XY: 0.00758 AC XY: 461 AN XY: 60834

Gnomad4 AFR AF: 0.00615

Gnomad4 AMR AF: 0.00769

Gnomad4 ASJ AF: 0.00553

Gnomad4 EAS AF: 0.0462

Gnomad4 SAS AF: 0.00909

Gnomad4 FIN AF: 0.00252

Gnomad4 NFE AF: 0.00661

Gnomad4 OTH AF: 0.00992

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: rs60726084; hg19: chr22-46191234;