22-45700063-T-C

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.392-219T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0536 in 152,040 control chromosomes in the GnomAD database, including 245 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.054 (245 hom., cov: 31)
• Consequence: ATXN10 NM_013236.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.57

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=-1.04).
• BP6: Variant 22-45700063-T-C is Benign according to our data. Variant chr22-45700063-T-C is described in ClinVar as [Benign]. Clinvar id is 1225212.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.077 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATXN10	NM_013236.4	c.392-219T>C		intron_variant		ENST00000252934.10
ATXN10	NM_001167621.2	c.200-219T>C		intron_variant
ATXN10	XM_047441314.1	c.392-219T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATXN10	ENST00000252934.10	c.392-219T>C		intron_variant		1	NM_013236.4	P1
ATXN10	ENST00000381061.8	c.200-219T>C		intron_variant		2
ATXN10	ENST00000470722.1	n.351-219T>C		intron_variant, non_coding_transcript_variant		3
ATXN10	ENST00000498009.5	n.566-219T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0536 AC: 8145 AN: 151920 Hom.: 245 Cov.: 31

Gnomad AFR AF: 0.0793

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0451

Gnomad ASJ AF: 0.0612

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0309

Gnomad FIN AF: 0.0654

Gnomad MID AF: 0.0256

Gnomad NFE AF: 0.0443

Gnomad OTH AF: 0.0484

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

GnomAD4 genome AF: 0.0536 AC: 8154 AN: 152040 Hom.: 245 Cov.: 31 AF XY: 0.0543 AC XY: 4036 AN XY: 74334

Gnomad4 AFR AF: 0.0793

Gnomad4 AMR AF: 0.0451

Gnomad4 ASJ AF: 0.0612

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.0311

Gnomad4 FIN AF: 0.0654

Gnomad4 NFE AF: 0.0444

Gnomad4 OTH AF: 0.0479

Alfa AF: 0.0494 Hom.: 28

Bravo AF: 0.0535

Asia WGS AF: 0.0170 AC: 59 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 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.11
DANN	Benign	0.15

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: rs9614506; hg19: chr22-46095943;