22-45739053-G-A

Variant names:

• chr22-45739053-G-A
• rs138170
• NM_013236.4:c.1003+214G>A

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.1003+214G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 152,158 control chromosomes in the GnomAD database, including 4,124 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.22 (4124 hom., cov: 32)
• Consequence: ATXN10 NM_013236.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.149

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=-0.88).
• BP6: Variant 22-45739053-G-A is Benign according to our data. Variant chr22-45739053-G-A is described in ClinVar as [Benign]. Clinvar id is 1257197.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.349 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATXN10	NM_013236.4	c.1003+214G>A		intron_variant	Intron 8 of 11	ENST00000252934.10	NP_037368.1
ATXN10	NM_001167621.2	c.811+214G>A		intron_variant	Intron 7 of 10		NP_001161093.1
ATXN10	XM_047441314.1	c.1003+214G>A		intron_variant	Intron 8 of 11		XP_047297270.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATXN10	ENST00000252934.10	c.1003+214G>A		intron_variant	Intron 8 of 11	1	NM_013236.4	ENSP00000252934.4

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33209 AN: 152040 Hom.: 4121 Cov.: 32

Gnomad AFR AF: 0.354

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.162

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.208

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.180

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.165

Gnomad OTH AF: 0.192

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

GnomAD4 genome AF: 0.218 AC: 33245 AN: 152158 Hom.: 4124 Cov.: 32 AF XY: 0.217 AC XY: 16145 AN XY: 74370

Gnomad4 AFR AF: 0.354

Gnomad4 AMR AF: 0.162

Gnomad4 ASJ AF: 0.155

Gnomad4 EAS AF: 0.209

Gnomad4 SAS AF: 0.150

Gnomad4 FIN AF: 0.180

Gnomad4 NFE AF: 0.165

Gnomad4 OTH AF: 0.190

Alfa AF: 0.169 Hom.: 4542

Bravo AF: 0.223

Asia WGS AF: 0.174 AC: 605 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.42
DANN	Benign	0.29

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: rs138170; hg19: chr22-46134933;