chr22-45672264-G-A

Variant names:

• chr22-45672264-G-A
• rs2071872
• NM_013236.4:c.116+85G>A

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.116+85G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 1,241,694 control chromosomes in the GnomAD database, including 17,600 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (1526 hom., cov: 32)
  • Exomes 𝑓: 0.17 (16074 hom.)
• Consequence: ATXN10 NM_013236.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.515
• Publications: 5 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant 22-45672264-G-A is Benign according to our data. Variant chr22-45672264-G-A is described in ClinVar as Benign. ClinVar VariationId is 1273409.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.182 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.116+85G>A		intron	N/A	NP_037368.1	Q9UBB4-1
	ATXN10	NM_001167621.2		c.116+85G>A		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.116+85G>A		intron	N/A	ENSP00000252934.4	Q9UBB4-1
	ATXN10	ENST00000381061.8	TSL:2	c.116+85G>A		intron	N/A	ENSP00000370449.4	Q9UBB4-2
	ATXN10	ENST00000498009.5	TSL:5	n.77G>A		non_coding_transcript_exon	Exon 1 of 6

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19268 AN: 151326 Hom.: 1524 Cov.: 32

Gnomad AFR AF: 0.0397

Gnomad AMI AF: 0.168

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.142

Gnomad EAS AF: 0.192

Gnomad SAS AF: 0.133

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.0994

Gnomad NFE AF: 0.168

Gnomad OTH AF: 0.121

GnomAD4 exome AF: 0.169 AC: 184082 AN: 1090260 Hom.: 16074 Cov.: 23 AF XY: 0.169 AC XY: 88664 AN XY: 523538

African (AFR) AF: 0.0329 AC: 694 AN: 21074

American (AMR) AF: 0.149 AC: 1039 AN: 6968

Ashkenazi Jewish (ASJ) AF: 0.149 AC: 1915 AN: 12886

East Asian (EAS) AF: 0.297 AC: 6729 AN: 22644

South Asian (SAS) AF: 0.148 AC: 4825 AN: 32540

European-Finnish (FIN) AF: 0.177 AC: 4139 AN: 23324

Middle Eastern (MID) AF: 0.144 AC: 408 AN: 2832

European-Non Finnish (NFE) AF: 0.170 AC: 157649 AN: 925344

Other (OTH) AF: 0.157 AC: 6684 AN: 42648

GnomAD4 genome AF: 0.127 AC: 19275 AN: 151434 Hom.: 1526 Cov.: 32 AF XY: 0.127 AC XY: 9428 AN XY: 73994

African (AFR) AF: 0.0396 AC: 1639 AN: 41410

American (AMR) AF: 0.129 AC: 1961 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.142 AC: 490 AN: 3462

East Asian (EAS) AF: 0.192 AC: 970 AN: 5044

South Asian (SAS) AF: 0.134 AC: 641 AN: 4800

European-Finnish (FIN) AF: 0.165 AC: 1726 AN: 10452

Middle Eastern (MID) AF: 0.110 AC: 32 AN: 290

European-Non Finnish (NFE) AF: 0.168 AC: 11411 AN: 67746

Other (OTH) AF: 0.121 AC: 253 AN: 2098

Alfa AF: 0.151 Hom.: 249

Bravo AF: 0.121

Asia WGS AF: 0.138 AC: 472 AN: 3442

ClinVar

ClinVar submissions as Germline

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	-0.61
CADD	Benign	10
DANN	Benign	0.97
PhyloP100		0.52
PromoterAI		-0.020	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.6
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: rs2071872; hg19: chr22-46068144;