22-45672264-G-A

Position:

• chr22-45672264-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000252934.10(ATXN10):​c.116+85G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 1,241,694 control chromosomes in the GnomAD database, including 17,600 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (1526 hom., cov: 32)
  • Exomes 𝑓: 0.17 (16074 hom.)
• Consequence: ATXN10 ENST00000252934.10 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.515

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant 22-45672264-G-A is Benign according to our data. Variant chr22-45672264-G-A is described in ClinVar as [Benign]. Clinvar id is 1273409.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATXN10	NM_013236.4	c.116+85G>A		intron_variant		ENST00000252934.10	NP_037368.1
ATXN10	NM_001167621.2	c.116+85G>A		intron_variant			NP_001161093.1
ATXN10	XM_047441314.1	c.116+85G>A		intron_variant			XP_047297270.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATXN10	ENST00000252934.10	c.116+85G>A		intron_variant		1	NM_013236.4	ENSP00000252934	P1
	ENST00000623075.1	n.15246G>A		non_coding_transcript_exon_variant	1/1
ATXN10	ENST00000381061.8	c.116+85G>A		intron_variant		2		ENSP00000370449
ATXN10	ENST00000498009.5	n.77G>A		non_coding_transcript_exon_variant	1/6	5

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19268 AN: 151326 Hom.: 1524 Cov.: 32

Gnomad AFR AF: 0.0397

Gnomad AMI AF: 0.168

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.142

Gnomad EAS AF: 0.192

Gnomad SAS AF: 0.133

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.0994

Gnomad NFE AF: 0.168

Gnomad OTH AF: 0.121

GnomAD4 exome AF: 0.169 AC: 184082 AN: 1090260 Hom.: 16074 Cov.: 23 AF XY: 0.169 AC XY: 88664 AN XY: 523538

Gnomad4 AFR exome AF: 0.0329

Gnomad4 AMR exome AF: 0.149

Gnomad4 ASJ exome AF: 0.149

Gnomad4 EAS exome AF: 0.297

Gnomad4 SAS exome AF: 0.148

Gnomad4 FIN exome AF: 0.177

Gnomad4 NFE exome AF: 0.170

Gnomad4 OTH exome AF: 0.157

GnomAD4 genome AF: 0.127 AC: 19275 AN: 151434 Hom.: 1526 Cov.: 32 AF XY: 0.127 AC XY: 9428 AN XY: 73994

Gnomad4 AFR AF: 0.0396

Gnomad4 AMR AF: 0.129

Gnomad4 ASJ AF: 0.142

Gnomad4 EAS AF: 0.192

Gnomad4 SAS AF: 0.134

Gnomad4 FIN AF: 0.165

Gnomad4 NFE AF: 0.168

Gnomad4 OTH AF: 0.121

Alfa AF: 0.151 Hom.: 249

Bravo AF: 0.121

Asia WGS AF: 0.138 AC: 472 AN: 3442

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	10
DANN	Benign	0.97
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.6

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs2071872; hg19: chr22-46068144;