9-32984639-C-G

Variant names:

• chr9-32984639-C-G
• NM_001195248.2:c.762G>C
• APTX p.Pro254Pro

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_001195248.2(APTX):​c.762G>C​(p.Pro254Pro) variant causes a synonymous 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. Synonymous variant affecting the same amino acid position (i.e. P254P) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: APTX NM_001195248.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.690
• 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BP7: Synonymous conserved (PhyloP=0.69 with no splicing effect.

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.762G>C	p.Pro254Pro	synonymous	Exon 6 of 8	NP_001182177.2	Q7Z2E3-7
	APTX	NM_001195249.2		c.762G>C	p.Pro254Pro	synonymous	Exon 6 of 8	NP_001182178.1	Q7Z2E3-7
	APTX	NM_001368995.1		c.762G>C	p.Pro254Pro	synonymous	Exon 6 of 8	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.762G>C	p.Pro254Pro	synonymous	Exon 6 of 8	ENSP00000369145.2	Q7Z2E3-7
	APTX	ENST00000379819.6	TSL:1	c.762G>C	p.Pro254Pro	synonymous	Exon 7 of 9	ENSP00000369147.2	Q7Z2E3-7
	APTX	ENST00000463596.6	TSL:1	c.762G>C	p.Pro254Pro	synonymous	Exon 6 of 8	ENSP00000419846.1	Q7Z2E3-7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	5.9
DANN	Benign	0.69
PhyloP100		0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		Details are displayed if max score is > 0.2

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: chr9-32984637;