chr22-45718364-C-T

Variant names:

• chr22-45718364-C-T
• rs2071852
• NM_013236.4:c.648-49C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_013236.4(ATXN10):​c.648-49C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 1,423,964 control chromosomes in the GnomAD database, including 18,777 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.17 (2578 hom., cov: 32)
  • Exomes 𝑓: 0.16 (16199 hom.)
• Consequence: ATXN10 NM_013236.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0840
• Publications: 12 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 22-45718364-C-T is Benign according to our data. Variant chr22-45718364-C-T is described in ClinVar as Benign. ClinVar VariationId is 1232451.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.243 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.648-49C>T		intron	N/A	NP_037368.1	Q9UBB4-1
	ATXN10	NM_001167621.2		c.456-49C>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.648-49C>T		intron	N/A	ENSP00000252934.4	Q9UBB4-1
	ATXN10	ENST00000381061.8	TSL:2	c.456-49C>T		intron	N/A	ENSP00000370449.4	Q9UBB4-2
	ATXN10	ENST00000476998.5	TSL:3	n.127-49C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26506 AN: 151952 Hom.: 2563 Cov.: 32

Gnomad AFR AF: 0.246

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.221

Gnomad EAS AF: 0.0558

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.176

GnomAD2 exomes AF: 0.140 AC: 34984 AN: 250756 AF XY: 0.141

Gnomad AFR exome AF: 0.244

Gnomad AMR exome AF: 0.0839

Gnomad ASJ exome AF: 0.211

Gnomad EAS exome AF: 0.0491

Gnomad FIN exome AF: 0.144

Gnomad NFE exome AF: 0.152

Gnomad OTH exome AF: 0.162

GnomAD4 exome AF: 0.155 AC: 197595 AN: 1271894 Hom.: 16199 Cov.: 19 AF XY: 0.155 AC XY: 99489 AN XY: 642948

African (AFR) AF: 0.257 AC: 7606 AN: 29628

American (AMR) AF: 0.0896 AC: 3980 AN: 44396

Ashkenazi Jewish (ASJ) AF: 0.211 AC: 5275 AN: 24958

East Asian (EAS) AF: 0.0725 AC: 2805 AN: 38714

South Asian (SAS) AF: 0.126 AC: 10359 AN: 82306

European-Finnish (FIN) AF: 0.144 AC: 7648 AN: 53222

Middle Eastern (MID) AF: 0.200 AC: 1074 AN: 5380

European-Non Finnish (NFE) AF: 0.160 AC: 149961 AN: 939204

Other (OTH) AF: 0.164 AC: 8887 AN: 54086

GnomAD4 genome AF: 0.175 AC: 26563 AN: 152070 Hom.: 2578 Cov.: 32 AF XY: 0.173 AC XY: 12894 AN XY: 74330

African (AFR) AF: 0.247 AC: 10238 AN: 41478

American (AMR) AF: 0.134 AC: 2044 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.221 AC: 769 AN: 3472

East Asian (EAS) AF: 0.0557 AC: 289 AN: 5186

South Asian (SAS) AF: 0.113 AC: 544 AN: 4822

European-Finnish (FIN) AF: 0.141 AC: 1488 AN: 10570

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.157 AC: 10671 AN: 67954

Other (OTH) AF: 0.176 AC: 370 AN: 2108

Alfa AF: 0.164 Hom.: 3588

Bravo AF: 0.176

Asia WGS AF: 0.0920 AC: 321 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	-0.89
CADD	Benign	1.0
DANN	Benign	0.19
PhyloP100		-0.084
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: rs2071852; hg19: chr22-46114244; COSMIC: COSV53297130; COSMIC: COSV53297130;