22-45671813-C-T

Variant names:

• chr22-45671813-C-T
• rs144270457
• ENST00000381061.8:c.-251C>T

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BS1 BS2

The ENST00000381061.8(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 ENST00000381061.8 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.29
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• spinocerebellar ataxia type 10

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

ENSG00000280383 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High AC in GnomAd4 at 5633 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000381061.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATXN10	NM_013236.4	MANE Select	c.-251C>T		upstream_gene	N/A	NP_037368.1	Q9UBB4-1
	ATXN10	NM_001167621.2		c.-251C>T		upstream_gene	N/A	NP_001161093.1	Q9UBB4-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATXN10	ENST00000381061.8	TSL:2	c.-251C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 11	ENSP00000370449.4	Q9UBB4-2
	ATXN10	ENST00000381061.8	TSL:2	c.-251C>T		5_prime_UTR	Exon 1 of 11	ENSP00000370449.4	Q9UBB4-2
	ENSG00000280383	ENST00000623075.1	TSL:6	n.14795C>T		non_coding_transcript_exon	Exon 1 of 1

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

African (AFR) AF: 0.0330 AC: 135 AN: 4086

American (AMR) AF: 0.0311 AC: 133 AN: 4278

Ashkenazi Jewish (ASJ) AF: 0.0642 AC: 377 AN: 5872

East Asian (EAS) AF: 0.00 AC: 0 AN: 12874

South Asian (SAS) AF: 0.0255 AC: 391 AN: 15344

European-Finnish (FIN) AF: 0.0585 AC: 767 AN: 13112

Middle Eastern (MID) AF: 0.0471 AC: 43 AN: 912

European-Non Finnish (NFE) AF: 0.0397 AC: 4472 AN: 112636

Other (OTH) AF: 0.0376 AC: 417 AN: 11078

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

African (AFR) AF: 0.0309 AC: 1281 AN: 41494

American (AMR) AF: 0.0384 AC: 587 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0602 AC: 209 AN: 3472

East Asian (EAS) AF: 0.000197 AC: 1 AN: 5084

South Asian (SAS) AF: 0.0192 AC: 92 AN: 4798

European-Finnish (FIN) AF: 0.0652 AC: 691 AN: 10600

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0396 AC: 2690 AN: 67890

Other (OTH) AF: 0.0359 AC: 76 AN: 2116

Alfa AF: 0.0352 Hom.: 13

Bravo AF: 0.0351

Asia WGS AF: 0.00779 AC: 27 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	14
DANN	Benign	0.95
PhyloP100		-1.3
PromoterAI		0.0012	Neutral
Mutation Taster		=300/0	polymorphism

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

Other links and lift over

dbSNP: rs144270457; hg19: chr22-46067693;