22-45729600-G-T

Variant names:

• chr22-45729600-G-T
• rs141434930
• NM_013236.4:c.894+10G>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_013236.4(ATXN10):​c.894+10G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00593 in 1,613,894 control chromosomes in the GnomAD database, including 38 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0044 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0061 (34 hom.)
• Consequence: ATXN10 NM_013236.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:3
• Conservation: PhyloP100: 0.514

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

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 22-45729600-G-T is Benign according to our data. Variant chr22-45729600-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 1285177.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr22-45729600-G-T is described in Lovd as [Likely_benign].
• BS2: High AC in GnomAd4 at 673 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATXN10	NM_013236.4	c.894+10G>T		intron_variant	Intron 7 of 11	ENST00000252934.10	NP_037368.1
ATXN10	NM_001167621.2	c.702+10G>T		intron_variant	Intron 6 of 10		NP_001161093.1
ATXN10	XM_047441314.1	c.894+10G>T		intron_variant	Intron 7 of 11		XP_047297270.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATXN10	ENST00000252934.10	c.894+10G>T		intron_variant	Intron 7 of 11	1	NM_013236.4	ENSP00000252934.4

Frequencies

GnomAD3 genomes AF: 0.00444 AC: 675 AN: 152130 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.00126

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00347

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00186

Gnomad FIN AF: 0.00359

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00756

Gnomad OTH AF: 0.00335

GnomAD2 exomes AF: 0.00423 AC: 1063 AN: 251280 AF XY: 0.00457

Gnomad AFR exome AF: 0.000800

Gnomad AMR exome AF: 0.00260

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00408

Gnomad NFE exome AF: 0.00705

Gnomad OTH exome AF: 0.00424

GnomAD4 exome AF: 0.00608 AC: 8892 AN: 1461646 Hom.: 34 Cov.: 31 AF XY: 0.00614 AC XY: 4461 AN XY: 727124

Gnomad4 AFR exome AF: 0.000926 AC: 31 AN: 33476

Gnomad4 AMR exome AF: 0.00250 AC: 112 AN: 44720

Gnomad4 ASJ exome AF: 0.000191 AC: 5 AN: 26132

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 39692

Gnomad4 SAS exome AF: 0.00169 AC: 146 AN: 86248

Gnomad4 FIN exome AF: 0.00428 AC: 228 AN: 53310

Gnomad4 NFE exome AF: 0.00722 AC: 8030 AN: 1111910

Gnomad4 Remaining exome AF: 0.00560 AC: 338 AN: 60392

GnomAD4 genome AF: 0.00442 AC: 673 AN: 152248 Hom.: 4 Cov.: 32 AF XY: 0.00406 AC XY: 302 AN XY: 74456

Gnomad4 AFR AF: 0.00125 AC: 0.00125187 AN: 0.00125187

Gnomad4 AMR AF: 0.00347 AC: 0.00346677 AN: 0.00346677

Gnomad4 ASJ AF: 0.000576 AC: 0.000576369 AN: 0.000576369

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.00186 AC: 0.00186413 AN: 0.00186413

Gnomad4 FIN AF: 0.00359 AC: 0.00358626 AN: 0.00358626

Gnomad4 NFE AF: 0.00753 AC: 0.00752676 AN: 0.00752676

Gnomad4 OTH AF: 0.00331 AC: 0.00331126 AN: 0.00331126

Alfa AF: 0.00521 Hom.: 1

Bravo AF: 0.00413

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:3

-

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.4
DANN	Benign	0.46
Mutation Taster		=100/0	polymorphism

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: rs141434930; hg19: chr22-46125480;