NM_001195248.2:c.742_744delTTGinsCTA

Variant names:

• chr9-32984657-CAA-TAG
• NM_001195248.2:c.742_744delTTGinsCTA
• APTX p.249

Variant summary

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

The NM_001195248.2(APTX):​c.742_744delTTGinsCTA​(p.249) variant causes a synonymous change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L248L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: APTX NM_001195248.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.21
• Publications: 0 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: Labcorp Genetics (formerly Invitae), G2P, Orphanet, Genomics England PanelApp

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001195248.2. 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
	APTX	NM_001195248.2	MANE Select	c.742_744delTTGinsCTA	p.249	synonymous	N/A	NP_001182177.2	Q7Z2E3-7
	APTX	NM_001195249.2		c.742_744delTTGinsCTA	p.249	synonymous	N/A	NP_001182178.1	Q7Z2E3-7
	APTX	NM_001368995.1		c.742_744delTTGinsCTA	p.249	synonymous	N/A	NP_001355924.1	Q7Z2E3-7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APTX	ENST00000379817.7	TSL:1 MANE Select	c.742_744delTTGinsCTA	p.249	synonymous	N/A	ENSP00000369145.2	Q7Z2E3-7
	APTX	ENST00000379819.6	TSL:1	c.742_744delTTGinsCTA	p.249	synonymous	N/A	ENSP00000369147.2	Q7Z2E3-7
	APTX	ENST00000463596.6	TSL:1	c.742_744delTTGinsCTA	p.249	synonymous	N/A	ENSP00000419846.1	Q7Z2E3-7

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

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		6.2

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr9-32984655;