chr22-45700117-A-G

Variant names:

• chr22-45700117-A-G
• rs16994442
• NM_013236.4:c.392-165A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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]

ATXN10 Gene-Disease associations (from GenCC):

• spinocerebellar ataxia type 10

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013236.4. 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
	ATXN10	NM_013236.4	MANE Select	c.392-165A>G		intron	N/A	NP_037368.1	Q9UBB4-1
	ATXN10	NM_001167621.2		c.200-165A>G		intron	N/A	NP_001161093.1	Q9UBB4-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATXN10	ENST00000252934.10	TSL:1 MANE Select	c.392-165A>G		intron	N/A	ENSP00000252934.4	Q9UBB4-1
	ATXN10	ENST00000381061.8	TSL:2	c.200-165A>G		intron	N/A	ENSP00000370449.4	Q9UBB4-2
	ATXN10	ENST00000470722.1	TSL:3	n.351-165A>G		intron	N/A

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

African (AFR) AF: 0.0576 AC: 2393 AN: 41574

American (AMR) AF: 0.0818 AC: 1251 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.157 AC: 545 AN: 3470

East Asian (EAS) AF: 0.0997 AC: 516 AN: 5176

South Asian (SAS) AF: 0.0944 AC: 456 AN: 4830

European-Finnish (FIN) AF: 0.0721 AC: 765 AN: 10606

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.112 AC: 7643 AN: 68030

Other (OTH) AF: 0.110 AC: 232 AN: 2114

Alfa AF: 0.0953 Hom.: 115

Bravo AF: 0.0900

Asia WGS AF: 0.0910 AC: 316 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.7
DANN	Benign	0.81
PhyloP100		0.11
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs16994442; hg19: chr22-46095997;