chr22-45671813-C-T

Position:

• chr22-45671813-C-T

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BS1 BS2

The ENST00000381061(ATXN10):​c.-251C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0372 in 332,136 control chromosomes in the GnomAD database, including 293 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.037 (122 hom., cov: 31)
  • Exomes 𝑓: 0.037 (171 hom.)
• Consequence: ATXN10 ENST00000381061 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.29

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]

ENSG00000280383 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.28).
• BP6: Variant 22-45671813-C-T is Benign according to our data. Variant chr22-45671813-C-T is described in ClinVar as [Benign]. Clinvar id is 1228260.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0371 (5633/151944) while in subpopulation NFE AF= 0.0396 (2690/67890). AF 95% confidence interval is 0.0384. There are 122 homozygotes in gnomad4. There are 2865 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 5633 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.45671813C>T		intergenic_region
ATXN10	NM_013236.4	c.-251C>T		upstream_gene_variant		ENST00000252934.10	NP_037368.1
ATXN10	NM_001167621.2	c.-251C>T		upstream_gene_variant			NP_001161093.1
ATXN10	XM_047441314.1	c.-251C>T		upstream_gene_variant			XP_047297270.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATXN10	ENST00000381061	c.-251C>T		5_prime_UTR_premature_start_codon_gain_variant	1/11	2		ENSP00000370449.4
ATXN10	ENST00000381061	c.-251C>T		5_prime_UTR_variant	1/11	2		ENSP00000370449.4
ENSG00000280383	ENST00000623075.1	n.14795C>T		non_coding_transcript_exon_variant	1/1	6
ATXN10	ENST00000252934.10	c.-251C>T		upstream_gene_variant		1	NM_013236.4	ENSP00000252934.4

Frequencies

GnomAD3 genomes AF: 0.0370 AC: 5624 AN: 151828 Hom.: 122 Cov.: 31

Gnomad AFR AF: 0.0308

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0384

Gnomad ASJ AF: 0.0602

Gnomad EAS AF: 0.000196

Gnomad SAS AF: 0.0187

Gnomad FIN AF: 0.0652

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0396

Gnomad OTH AF: 0.0358

GnomAD4 exome AF: 0.0374 AC: 6735 AN: 180192 Hom.: 171 Cov.: 2 AF XY: 0.0371 AC XY: 3504 AN XY: 94472

Gnomad4 AFR exome AF: 0.0330

Gnomad4 AMR exome AF: 0.0311

Gnomad4 ASJ exome AF: 0.0642

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0255

Gnomad4 FIN exome AF: 0.0585

Gnomad4 NFE exome AF: 0.0397

Gnomad4 OTH exome AF: 0.0376

GnomAD4 genome AF: 0.0371 AC: 5633 AN: 151944 Hom.: 122 Cov.: 31 AF XY: 0.0386 AC XY: 2865 AN XY: 74268

Gnomad4 AFR AF: 0.0309

Gnomad4 AMR AF: 0.0384

Gnomad4 ASJ AF: 0.0602

Gnomad4 EAS AF: 0.000197

Gnomad4 SAS AF: 0.0192

Gnomad4 FIN AF: 0.0652

Gnomad4 NFE AF: 0.0396

Gnomad4 OTH AF: 0.0359

Alfa AF: 0.0352 Hom.: 13

Bravo AF: 0.0351

Asia WGS AF: 0.00779 AC: 27 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 20, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	14
DANN	Benign	0.95

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: rs144270457; hg19: chr22-46067693;