9-32978808-C-T

Position:

• chr9-32978808-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001195248.2(APTX):​c.771-4247G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 152,086 control chromosomes in the GnomAD database, including 2,461 homozygotes. 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: 𝑓 0.17 (2461 hom., cov: 32)
• Consequence: APTX NM_001195248.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.212

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.392 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
APTX	NM_001195248.2	c.771-4247G>A		intron_variant		ENST00000379817.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
APTX	ENST00000379817.7	c.771-4247G>A		intron_variant		1	NM_001195248.2	P1

Frequencies

GnomAD3 genomes AF: 0.172 AC: 26095 AN: 151968 Hom.: 2454 Cov.: 32

Gnomad AFR AF: 0.214

Gnomad AMI AF: 0.0768

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.142

Gnomad EAS AF: 0.407

Gnomad SAS AF: 0.233

Gnomad FIN AF: 0.102

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.141

Gnomad OTH AF: 0.158

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

GnomAD4 genome AF: 0.172 AC: 26149 AN: 152086 Hom.: 2461 Cov.: 32 AF XY: 0.174 AC XY: 12956 AN XY: 74356

Gnomad4 AFR AF: 0.214

Gnomad4 AMR AF: 0.158

Gnomad4 ASJ AF: 0.142

Gnomad4 EAS AF: 0.407

Gnomad4 SAS AF: 0.234

Gnomad4 FIN AF: 0.102

Gnomad4 NFE AF: 0.141

Gnomad4 OTH AF: 0.159

Alfa AF: 0.145 Hom.: 2262

Bravo AF: 0.175

Asia WGS AF: 0.301 AC: 1045 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.6
DANN	Benign	0.60

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

Publications

LitVar

Other links and lift over

dbSNP: rs10971259; hg19: chr9-32978806; COSMIC: COSV58928119; COSMIC: COSV58928119;