Genetic Variant NM_001195248.2:c.484-3_484-2insGTTTTTTTTT (chr9-32986032-T-TAAAAAAAAAC) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001195248.2(APTX):c.484-3_484-2insGTTTTTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 0)

Exomes 𝑓: 0.00026 ( 2 hom. )

Failed GnomAD Quality Control

Consequence

APTX
NM_001195248.2 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.384

Publications

0 publications found

Variant links:

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

APTX links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APTX	NM_001195248.2 link	c.484-3_484-2insGTTTTTTTTT		splice_region_variant, intron_variant	Intron 4 of 7	ENST00000379817.7	NP_001182177.2	Q7Z2E3-7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APTX	ENST00000379817.7 link	c.484-3_484-2insGTTTTTTTTT		splice_region_variant, intron_variant	Intron 4 of 7	1	NM_001195248.2	ENSP00000369145.2		Q7Z2E3-7

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

14400

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000262

AC:

188

AN:

718864

Hom.:

Cov.:

AF XY:

0.000299

AC XY:

111

AN XY:

371608

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.000453

AC:

AN:

15458

American (AMR)

AF:

0.000806

AC:

AN:

24812

Ashkenazi Jewish (ASJ)

AF:

0.000248

AC:

AN:

16120

East Asian (EAS)

AF:

0.000941

AC:

AN:

24452

South Asian (SAS)

AF:

0.000835

AC:

AN:

51520

European-Finnish (FIN)

AF:

0.000105

AC:

AN:

28444

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2308

European-Non Finnish (NFE)

AF:

0.000153

AC:

AN:

523950

Other (OTH)

AF:

0.000252

AC:

AN:

31800

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.400

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

14400

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

6660

African (AFR)

AF:

0.00

AC:

AN:

5156

American (AMR)

AF:

0.00

AC:

AN:

1192

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

320

East Asian (EAS)

AF:

0.00

AC:

AN:

468

South Asian (SAS)

AF:

0.00

AC:

AN:

390

European-Finnish (FIN)

AF:

0.00

AC:

AN:

556

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

6094

Other (OTH)

AF:

0.00

AC:

AN:

118

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.38

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over