22-45700117-A-G

Position:

• chr22-45700117-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_013236.4(ATXN10):​c.392-165A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0915 in 152,300 control chromosomes in the GnomAD database, including 715 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.092 (715 hom., cov: 32)
• Consequence: ATXN10 NM_013236.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.108

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 22-45700117-A-G is Benign according to our data. Variant chr22-45700117-A-G is described in ClinVar as [Benign]. Clinvar id is 1251188.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATXN10	NM_013236.4	c.392-165A>G		intron_variant		ENST00000252934.10	NP_037368.1
ATXN10	NM_001167621.2	c.200-165A>G		intron_variant			NP_001161093.1
ATXN10	XM_047441314.1	c.392-165A>G		intron_variant			XP_047297270.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATXN10	ENST00000252934.10	c.392-165A>G		intron_variant		1	NM_013236.4	ENSP00000252934	P1
ATXN10	ENST00000381061.8	c.200-165A>G		intron_variant		2		ENSP00000370449
ATXN10	ENST00000470722.1	n.351-165A>G		intron_variant, non_coding_transcript_variant		3
ATXN10	ENST00000498009.5	n.566-165A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0916 AC: 13943 AN: 152182 Hom.: 715 Cov.: 32

Gnomad AFR AF: 0.0577

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.0819

Gnomad ASJ AF: 0.157

Gnomad EAS AF: 0.0995

Gnomad SAS AF: 0.0947

Gnomad FIN AF: 0.0721

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.110

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

GnomAD4 genome AF: 0.0915 AC: 13941 AN: 152300 Hom.: 715 Cov.: 32 AF XY: 0.0895 AC XY: 6663 AN XY: 74470

Gnomad4 AFR AF: 0.0576

Gnomad4 AMR AF: 0.0818

Gnomad4 ASJ AF: 0.157

Gnomad4 EAS AF: 0.0997

Gnomad4 SAS AF: 0.0944

Gnomad4 FIN AF: 0.0721

Gnomad4 NFE AF: 0.112

Gnomad4 OTH AF: 0.110

Alfa AF: 0.0966 Hom.: 114

Bravo AF: 0.0900

Asia WGS AF: 0.0910 AC: 316 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 18, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.7
DANN	Benign	0.81

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: rs16994442; hg19: chr22-46095997;