rs199766375

Variant names:

• chr22-45700294-G-A
• rs199766375
• NM_013236.4:c.404G>A

Your query was ambiguous. Multiple possible variants found:

• chr22-45700294-G-A
• chr22-45700294-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_013236.4(ATXN10):​c.404G>A​(p.Gly135Asp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G135V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ATXN10 NM_013236.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.43
• 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: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.806

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.404G>A	p.Gly135Asp	missense	Exon 4 of 12	NP_037368.1	Q9UBB4-1
	ATXN10	NM_001167621.2		c.212G>A	p.Gly71Asp	missense	Exon 3 of 11	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.404G>A	p.Gly135Asp	missense	Exon 4 of 12	ENSP00000252934.4	Q9UBB4-1
	ATXN10	ENST00000381061.8	TSL:2	c.212G>A	p.Gly71Asp	missense	Exon 3 of 11	ENSP00000370449.4	Q9UBB4-2
	ATXN10	ENST00000470722.1	TSL:3	n.363G>A		non_coding_transcript_exon	Exon 4 of 4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Pathogenic	0.14
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.56	D
Eigen	Uncertain	0.68
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.025	D
MetaRNN	Pathogenic	0.81	D
MetaSVM	Benign	-0.75	T
MutationAssessor	Benign	1.9	L
PhyloP100		6.4
PrimateAI	Uncertain	0.78	T
PROVEAN	Uncertain	-3.1	D
REVEL	Uncertain	0.39
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.010	D
Polyphen		1.0	D
Vest4		0.90
MutPred		0.68		Loss of helix (P = 0.0376)
MVP		0.75
MPC		0.27
ClinPred		0.97	D
GERP RS		5.9
Varity_R		0.73
gMVP		0.81
Mutation Taster		=58/42	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs199766375; hg19: chr22-46096174;