rs2071851

Variant names:

• chr22-45718267-C-T
• rs2071851
• NM_013236.4:c.648-146C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_013236.4(ATXN10):​c.648-146C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 732,102 control chromosomes in the GnomAD database, including 12,074 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.14 (1978 hom., cov: 32)
  • Exomes 𝑓: 0.18 (10096 hom.)
• Consequence: ATXN10 NM_013236.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.549
• Publications: 2 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

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 22-45718267-C-T is Benign according to our data. Variant chr22-45718267-C-T is described in ClinVar as Benign. ClinVar VariationId is 1296745.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.213 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013236.4. 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.648-146C>T		intron	N/A	NP_037368.1	Q9UBB4-1
	ATXN10	NM_001167621.2		c.456-146C>T		intron	N/A	NP_001161093.1	Q9UBB4-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATXN10	ENST00000252934.10	TSL:1 MANE Select	c.648-146C>T		intron	N/A	ENSP00000252934.4	Q9UBB4-1
	ATXN10	ENST00000381061.8	TSL:2	c.456-146C>T		intron	N/A	ENSP00000370449.4	Q9UBB4-2
	ATXN10	ENST00000476998.5	TSL:3	n.127-146C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21633 AN: 151848 Hom.: 1976 Cov.: 32

Gnomad AFR AF: 0.0363

Gnomad AMI AF: 0.239

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.147

Gnomad EAS AF: 0.223

Gnomad SAS AF: 0.147

Gnomad FIN AF: 0.220

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.137

GnomAD4 exome AF: 0.180 AC: 104552 AN: 580136 Hom.: 10096 AF XY: 0.178 AC XY: 56133 AN XY: 314802

African (AFR) AF: 0.0343 AC: 539 AN: 15704

American (AMR) AF: 0.143 AC: 4799 AN: 33444

Ashkenazi Jewish (ASJ) AF: 0.139 AC: 2495 AN: 17998

East Asian (EAS) AF: 0.279 AC: 9640 AN: 34594

South Asian (SAS) AF: 0.136 AC: 8231 AN: 60338

European-Finnish (FIN) AF: 0.216 AC: 9318 AN: 43096

Middle Eastern (MID) AF: 0.147 AC: 420 AN: 2852

European-Non Finnish (NFE) AF: 0.187 AC: 63994 AN: 341484

Other (OTH) AF: 0.167 AC: 5116 AN: 30626

GnomAD4 genome AF: 0.142 AC: 21637 AN: 151966 Hom.: 1978 Cov.: 32 AF XY: 0.144 AC XY: 10684 AN XY: 74262

African (AFR) AF: 0.0362 AC: 1500 AN: 41486

American (AMR) AF: 0.133 AC: 2034 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.147 AC: 510 AN: 3470

East Asian (EAS) AF: 0.223 AC: 1153 AN: 5162

South Asian (SAS) AF: 0.147 AC: 710 AN: 4814

European-Finnish (FIN) AF: 0.220 AC: 2310 AN: 10506

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.190 AC: 12882 AN: 67958

Other (OTH) AF: 0.136 AC: 287 AN: 2110

Alfa AF: 0.179 Hom.: 359

Bravo AF: 0.132

Asia WGS AF: 0.157 AC: 543 AN: 3476

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.9
DANN	Benign	0.44
PhyloP100		-0.55
Mutation Taster		=100/0	polymorphism (auto)

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: rs2071851; hg19: chr22-46114147;