Genetic Variant ATXN10:c.-251C>T (chr22-45671813-C-T) – ACMG Classification: Benign (-18 pts)

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.29

Variant links:

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]

ATXN10 links:

ENSG00000280383 (HGNC:):

ENSG00000280383 links:

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ACMG classification

Classification made for transcript

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	Effect	MANE	Protein	UniProt
ATXN10	NM_013236.4 link	c.-251C>T	upstream_gene_variant	ENST00000252934.10	NP_037368.1	Q9UBB4-1
ATXN10	NM_001167621.2 link	c.-251C>T	upstream_gene_variant		NP_001161093.1	Q9UBB4-2
ATXN10	XM_047441314.1 link	c.-251C>T	upstream_gene_variant		XP_047297270.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ATXN10	ENST00000381061 link	c.-251C>T	5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 11	2		ENSP00000370449.4	Q9UBB4-2
ATXN10	ENST00000381061 link	c.-251C>T	5_prime_UTR_variant	Exon 1 of 11	2		ENSP00000370449.4	Q9UBB4-2
ENSG00000280383	ENST00000623075.1 link	n.14795C>T	non_coding_transcript_exon_variant	Exon 1 of 1	6
ATXN10	ENST00000252934.10 link	c.-251C>T	upstream_gene_variant		1	NM_013236.4	ENSP00000252934.4	Q9UBB4-1

Frequencies

GnomAD3 genomes

AF:

0.0370

AC:

5624

AN:

151828

Hom.:

122

Cov.:

show subpopulations

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.:

AF XY:

0.0371

AC XY:

3504

AN XY:

94472

show subpopulations

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.:

AF XY:

0.0386

AC XY:

2865

AN XY:

74268

show subpopulations

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.:

Bravo

AF:

0.0351

Asia WGS

AF:

0.00779

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 20, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.28

CADD

Benign

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over