rs1160067775

Variant names:

• chr22-45672183-A-G
• rs1160067775
• NM_013236.4:c.116+4A>G

Your query was ambiguous. Multiple possible variants found:

• chr22-45672183-A-G
• chr22-45672183-A-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_013236.4(ATXN10):​c.116+4A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000726 in 1,377,092 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000073 (0 hom.)
• Consequence: ATXN10 NM_013236.4 splice_region, intron
• Scores: Splicing: ADA: 0.9904
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.310

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]

ENSG00000280383 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 10 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATXN10	NM_013236.4	c.116+4A>G		splice_region_variant, intron_variant	Intron 1 of 11	ENST00000252934.10	NP_037368.1
ATXN10	NM_001167621.2	c.116+4A>G		splice_region_variant, intron_variant	Intron 1 of 10		NP_001161093.1
ATXN10	XM_047441314.1	c.116+4A>G		splice_region_variant, intron_variant	Intron 1 of 11		XP_047297270.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATXN10	ENST00000252934.10	c.116+4A>G		splice_region_variant, intron_variant	Intron 1 of 11	1	NM_013236.4	ENSP00000252934.4
ATXN10	ENST00000381061.8	c.116+4A>G		splice_region_variant, intron_variant	Intron 1 of 10	2		ENSP00000370449.4
ENSG00000280383	ENST00000623075.1	n.15165A>G		non_coding_transcript_exon_variant	Exon 1 of 1	6
ATXN10	ENST00000498009.5	n.-5A>G		upstream_gene_variant		5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000770 AC: 1 AN: 129946 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 71224

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000420

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000726 AC: 10 AN: 1377092 Hom.: 0 Cov.: 31 AF XY: 0.00000294 AC XY: 2 AN XY: 679554

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000284

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000560

Gnomad4 OTH exome AF: 0.0000526

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	19
DANN	Benign	0.90
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	0.99
dbscSNV1_RF	Pathogenic	0.78
SpliceAI score (max)		0.17		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

Other links and lift over

dbSNP: rs1160067775; hg19: chr22-46068063;