9-33007413-T-G

Variant names:

• chr9-33007413-T-G
• rs10124051
• ENST00000468275.6:c.-5+17391A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000468275.6(APTX):​c.-5+17391A>C variant causes a intron 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: APTX ENST00000468275.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.617
• Publications: 5 publications found

Genes affected

APTX (HGNC:15984): (aprataxin) This gene encodes a member of the histidine triad (HIT) superfamily. The encoded protein may play a role in single-stranded DNA repair through its nucleotide-binding activity and its diadenosine polyphosphate hydrolase activity. Mutations in this gene have been associated with ataxia-ocular apraxia. Alternatively spliced transcript variants have been identified for this gene.[provided by RefSeq, Aug 2010]

APTX Gene-Disease associations (from GenCC):

• ataxia, early-onset, with oculomotor apraxia and hypoalbuminemia

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp

ENSG00000305836 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APTX	NM_001368995.1	c.-4-17518A>C		intron_variant	Intron 1 of 7		NP_001355924.1
APTX	NM_001368996.1	c.-4-17518A>C		intron_variant	Intron 1 of 7		NP_001355925.1
APTX	NM_001368997.1	c.-5+17391A>C		intron_variant	Intron 1 of 7		NP_001355926.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APTX	ENST00000468275.6	c.-5+17391A>C		intron_variant	Intron 1 of 7	1		ENSP00000420263.2
APTX	ENST00000436040.7	c.-4-17518A>C		intron_variant	Intron 1 of 6	1		ENSP00000400806.4
APTX	ENST00000460940.6	n.-4-17518A>C		intron_variant	Intron 1 of 6	1		ENSP00000418311.1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 1846

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.1
DANN	Benign	0.72
PhyloP100		-0.62

Splicing

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

Other links and lift over

dbSNP: rs10124051; hg19: chr9-33007411;