22-45672139-C-T

Position:

• chr22-45672139-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Moderate BP6 BP7 BS2

The ENST00000252934.10(ATXN10):​c.76C>T​(p.Leu26=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000228 in 1,540,232 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00062 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00019 (0 hom.)
• Consequence: ATXN10 ENST00000252934.10 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:2
• Conservation: PhyloP100: 0.501

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.22).
• BP6: Variant 22-45672139-C-T is Benign according to our data. Variant chr22-45672139-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1328012.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr22-45672139-C-T is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=0.501 with no splicing effect.
• BS2: High AC in GnomAd4 at 94 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATXN10	NM_013236.4	c.76C>T	p.Leu26=	synonymous_variant	1/12	ENST00000252934.10	NP_037368.1
ATXN10	NM_001167621.2	c.76C>T	p.Leu26=	synonymous_variant	1/11		NP_001161093.1
ATXN10	XM_047441314.1	c.76C>T	p.Leu26=	synonymous_variant	1/12		XP_047297270.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATXN10	ENST00000252934.10	c.76C>T	p.Leu26=	synonymous_variant	1/12	1	NM_013236.4	ENSP00000252934	P1
	ENST00000623075.1	n.15121C>T		non_coding_transcript_exon_variant	1/1
ATXN10	ENST00000381061.8	c.76C>T	p.Leu26=	synonymous_variant	1/11	2		ENSP00000370449
ATXN10	ENST00000498009.5			upstream_gene_variant		5

Frequencies

GnomAD3 genomes AF: 0.000618 AC: 94 AN: 152068 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00179

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00955

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.000306 AC: 42 AN: 137458 Hom.: 0 AF XY: 0.000214 AC XY: 16 AN XY: 74820

Gnomad AFR exome AF: 0.00298

Gnomad AMR exome AF: 0.000246

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000210

Gnomad OTH exome AF: 0.00144

GnomAD4 exome AF: 0.000185 AC: 257 AN: 1388046 Hom.: 0 Cov.: 31 AF XY: 0.000180 AC XY: 123 AN XY: 684946

Gnomad4 AFR exome AF: 0.00207

Gnomad4 AMR exome AF: 0.000225

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000127

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000137

Gnomad4 OTH exome AF: 0.000485

GnomAD4 genome AF: 0.000618 AC: 94 AN: 152186 Hom.: 0 Cov.: 32 AF XY: 0.000591 AC XY: 44 AN XY: 74410

Gnomad4 AFR AF: 0.00178

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000162

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.000641 Hom.: 0

Bravo AF: 0.000642

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: no assertion criteria provided

Submissions by phenotype

not provided Benign:2

Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.22
CADD	Benign	19
DANN	Uncertain	0.98

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: rs186793141; hg19: chr22-46068019;