9-32973311-C-T

Variant names:

• chr9-32973311-C-T
• rs113638548
• NM_001195248.2:c.*187G>A

Variant summary

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

The NM_001195248.2(APTX):​c.*187G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000169 in 591,416 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.0000017 (0 hom.)
• Consequence: APTX NM_001195248.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.904
• 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).

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.*187G>A		3_prime_UTR	Exon 8 of 8	NP_001182177.2	Q7Z2E3-7
	APTX	NM_001195249.2		c.*187G>A		3_prime_UTR	Exon 8 of 8	NP_001182178.1	Q7Z2E3-7
	APTX	NM_001368995.1		c.*187G>A		3_prime_UTR	Exon 8 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.*187G>A		3_prime_UTR	Exon 8 of 8	ENSP00000369145.2	Q7Z2E3-7
	APTX	ENST00000379819.6	TSL:1	c.*187G>A		3_prime_UTR	Exon 9 of 9	ENSP00000369147.2	Q7Z2E3-7
	APTX	ENST00000309615.8	TSL:1	c.*187G>A		3_prime_UTR	Exon 7 of 7	ENSP00000311547.4	Q7Z2E3-5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000169 AC: 1 AN: 591416 Hom.: 0 Cov.: 7 AF XY: 0.00 AC XY: 0 AN XY: 317316

African (AFR) AF: 0.00 AC: 0 AN: 16416

American (AMR) AF: 0.00 AC: 0 AN: 34016

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19794

East Asian (EAS) AF: 0.00 AC: 0 AN: 30664

South Asian (SAS) AF: 0.00 AC: 0 AN: 63150

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30836

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2454

European-Non Finnish (NFE) AF: 0.00000276 AC: 1 AN: 362820

Other (OTH) AF: 0.00 AC: 0 AN: 31266

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.97
DANN	Benign	0.43
PhyloP100		-0.90

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

Other links and lift over

dbSNP: rs113638548; hg19: chr9-32973309;