rs4830842

Positions:

• chrX-13318940-C-G
• chrX-13318940-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001135995.2(ATXN3L):​c.995G>C​(p.Gly332Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign 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. G332D) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 23)
• Consequence: ATXN3L NM_001135995.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.153

Genes affected

ATXN3L (HGNC:24173): (ataxin 3 like) This intronless gene may be a pseudogene (PMID:11450850). This gene is similar to the multi-exon gene which encodes ataxin 3 and contains a coding region which could encode a protein similar to ataxin 3. Mutations in the gene encoding ataxin 3 are associated with Machado-Joseph disease. [provided by RefSeq, Sep 2011]

GS1-600G8.3 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04407102).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATXN3L	NM_001135995.2	c.995G>C	p.Gly332Ala	missense_variant	1/1	ENST00000380622.5	NP_001129467.1
ATXN3L	NM_001387036.1	c.731G>C	p.Gly244Ala	missense_variant	2/2		NP_001373965.1
GS1-600G8.3	NR_046087.1	n.1449-68C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATXN3L	ENST00000380622.5	c.995G>C	p.Gly332Ala	missense_variant	1/1	6	NM_001135995.2	ENSP00000369996.2
GS1-600G8.3	ENST00000431486.1	n.1449-68C>G		intron_variant		1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-1.1
CADD	Benign	10
DANN	Benign	0.44
DEOGEN2	Benign	0.0050	T
FATHMM_MKL	Benign	0.0034	N
LIST_S2	Benign	0.26	T
M_CAP	Benign	0.0027	T
MetaRNN	Benign	0.044	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.010	N
REVEL	Benign	0.17
Sift	Benign	0.075	T
Sift4G	Benign	0.20	T
Polyphen		0.0	B
Vest4		0.051
MutPred		0.26		Gain of helix (P = 0.0425);
MVP		0.27
MPC		0.083
ClinPred		0.21	T
GERP RS		0.79
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.12
gMVP		0.019

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

Publications

LitVar

Other links and lift over

dbSNP: rs4830842; hg19: chrX-13337059;