NM_001195248.2:c.-4-239A>G

Variant names:

• chr9-32990134-T-C
• rs10813916
• NM_001195248.2:c.-4-239A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001195248.2(APTX):​c.-4-239A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 552,662 control chromosomes in the GnomAD database, including 12,432 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.19 (3129 hom., cov: 32)
  • Exomes 𝑓: 0.21 (9303 hom.)
• Consequence: APTX NM_001195248.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.729
• Publications: 7 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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 9-32990134-T-C is Benign according to our data. Variant chr9-32990134-T-C is described in ClinVar as [Benign]. Clinvar id is 1225499.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.228 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APTX	NM_001195248.2	c.-4-239A>G		intron_variant	Intron 1 of 7	ENST00000379817.7	NP_001182177.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APTX	ENST00000379817.7	c.-4-239A>G		intron_variant	Intron 1 of 7	1	NM_001195248.2	ENSP00000369145.2

Frequencies

GnomAD3 genomes AF: 0.195 AC: 29636 AN: 152142 Hom.: 3131 Cov.: 32

Gnomad AFR AF: 0.147

Gnomad AMI AF: 0.299

Gnomad AMR AF: 0.198

Gnomad ASJ AF: 0.278

Gnomad EAS AF: 0.0307

Gnomad SAS AF: 0.0952

Gnomad FIN AF: 0.227

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.231

Gnomad OTH AF: 0.211

GnomAD4 exome AF: 0.206 AC: 82376 AN: 400402 Hom.: 9303 Cov.: 3 AF XY: 0.201 AC XY: 42259 AN XY: 210572

African (AFR) AF: 0.149 AC: 1742 AN: 11670

American (AMR) AF: 0.196 AC: 3210 AN: 16364

Ashkenazi Jewish (ASJ) AF: 0.292 AC: 3686 AN: 12618

East Asian (EAS) AF: 0.0501 AC: 1393 AN: 27792

South Asian (SAS) AF: 0.107 AC: 4003 AN: 37462

European-Finnish (FIN) AF: 0.224 AC: 5661 AN: 25252

Middle Eastern (MID) AF: 0.275 AC: 497 AN: 1804

European-Non Finnish (NFE) AF: 0.234 AC: 57202 AN: 244008

Other (OTH) AF: 0.213 AC: 4982 AN: 23432

GnomAD4 genome AF: 0.195 AC: 29624 AN: 152260 Hom.: 3129 Cov.: 32 AF XY: 0.192 AC XY: 14269 AN XY: 74442

African (AFR) AF: 0.146 AC: 6085 AN: 41548

American (AMR) AF: 0.198 AC: 3022 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.278 AC: 964 AN: 3472

East Asian (EAS) AF: 0.0310 AC: 161 AN: 5194

South Asian (SAS) AF: 0.0945 AC: 456 AN: 4826

European-Finnish (FIN) AF: 0.227 AC: 2401 AN: 10600

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.231 AC: 15737 AN: 68014

Other (OTH) AF: 0.208 AC: 440 AN: 2112

Alfa AF: 0.226 Hom.: 5220

Bravo AF: 0.192

Asia WGS AF: 0.0760 AC: 265 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 09, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	2.8
DANN	Benign	0.83
PhyloP100		-0.73
Mutation Taster		=100/0	polymorphism (auto)

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: rs10813916; hg19: chr9-32990132;