rs16918936

Variant names:

• chr9-33009029-T-G
• rs16918936
• ENST00000468275.6:c.-5+15775A>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000468275.6(APTX):​c.-5+15775A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0396 in 152,300 control chromosomes in the GnomAD database, including 150 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 0.040 (150 hom., cov: 32)
• Consequence: APTX ENST00000468275.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.123
• Publications: 3 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

ENSG00000305836 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APTX	NM_001368995.1	c.-5+15971A>C		intron_variant	Intron 1 of 7		NP_001355924.1
APTX	NM_001368996.1	c.-5+15994A>C		intron_variant	Intron 1 of 7		NP_001355925.1
APTX	NM_001368997.1	c.-5+15775A>C		intron_variant	Intron 1 of 7		NP_001355926.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APTX	ENST00000468275.6	c.-5+15775A>C		intron_variant	Intron 1 of 7	1		ENSP00000420263.2
APTX	ENST00000436040.7	c.-5+15994A>C		intron_variant	Intron 1 of 6	1		ENSP00000400806.4
APTX	ENST00000460940.6	n.-5+15971A>C		intron_variant	Intron 1 of 6	1		ENSP00000418311.1

Frequencies

GnomAD3 genomes AF: 0.0397 AC: 6036 AN: 152182 Hom.: 150 Cov.: 32

Gnomad AFR AF: 0.0412

Gnomad AMI AF: 0.132

Gnomad AMR AF: 0.0579

Gnomad ASJ AF: 0.0239

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.0395

Gnomad FIN AF: 0.0333

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0297

Gnomad OTH AF: 0.0401

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

GnomAD4 genome AF: 0.0396 AC: 6038 AN: 152300 Hom.: 150 Cov.: 32 AF XY: 0.0418 AC XY: 3112 AN XY: 74470

African (AFR) AF: 0.0412 AC: 1712 AN: 41558

American (AMR) AF: 0.0579 AC: 886 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0239 AC: 83 AN: 3468

East Asian (EAS) AF: 0.112 AC: 583 AN: 5184

South Asian (SAS) AF: 0.0398 AC: 192 AN: 4830

European-Finnish (FIN) AF: 0.0333 AC: 353 AN: 10614

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0297 AC: 2021 AN: 68024

Other (OTH) AF: 0.0397 AC: 84 AN: 2116

Alfa AF: 0.0318 Hom.: 54

Bravo AF: 0.0418

Asia WGS AF: 0.0750 AC: 260 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	7.3
DANN	Benign	0.86
PhyloP100		-0.12

Splicing

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

Other links and lift over

dbSNP: rs16918936; hg19: chr9-33009027;