X-13319429-A-G

Position:

• chrX-13319429-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001135995.2(ATXN3L):​c.506T>C​(p.Leu169Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: ATXN3L NM_001135995.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.72

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATXN3L	NM_001135995.2	c.506T>C	p.Leu169Pro	missense_variant	1/1	ENST00000380622.5	NP_001129467.1
ATXN3L	NM_001387036.1	c.242T>C	p.Leu81Pro	missense_variant	2/2		NP_001373965.1
GS1-600G8.3	NR_046087.1	n.1870A>G		non_coding_transcript_exon_variant	16/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATXN3L	ENST00000380622.5	c.506T>C	p.Leu169Pro	missense_variant	1/1	6	NM_001135995.2	ENSP00000369996.2
GS1-600G8.3	ENST00000431486.1	n.1870A>G		non_coding_transcript_exon_variant	16/17	1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 29, 2024

The c.506T>C (p.L169P) alteration is located in exon 1 (coding exon 1) of the ATXN3L gene. This alteration results from a T to C substitution at nucleotide position 506, causing the leucine (L) at amino acid position 169 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Benign	-0.085	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.27	T;.
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Pathogenic	0.99	D;D
M_CAP	Benign	0.0091	T
MetaRNN	Uncertain	0.51	D;D
MetaSVM	Benign	-0.94	T
MutationAssessor	Pathogenic	3.1	M;.
PrimateAI	Benign	0.40	T
PROVEAN	Pathogenic	-6.5	D;.
REVEL	Benign	0.23
Sift	Pathogenic	0.0	D;.
Sift4G	Pathogenic	0.0010	D;D
Polyphen		1.0	D;.
Vest4		0.41
MutPred		0.55		Gain of disorder (P = 0.0394);.;
MVP		0.46
MPC		0.54
ClinPred		1.0	D
GERP RS		0.65
Varity_R		0.92
gMVP		0.84

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-13337548;