chr9-32987709-G-A

Variant names:

• chr9-32987709-G-A
• rs79254654
• NM_001195248.2:c.318C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001195248.2(APTX):​c.318C>T​(p.Asn106Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00141 in 1,614,130 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0077 (12 hom., cov: 32)
  • Exomes 𝑓: 0.00075 (13 hom.)
• Consequence: APTX NM_001195248.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -0.301
• Publications: 4 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: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 9-32987709-G-A is Benign according to our data. Variant chr9-32987709-G-A is described in ClinVar as Benign. ClinVar VariationId is 136413.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.301 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00767 (1167/152240) while in subpopulation AFR AF = 0.0269 (1116/41518). AF 95% confidence interval is 0.0256. There are 12 homozygotes in GnomAd4. There are 541 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 12 AR gene

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.318C>T	p.Asn106Asn	synonymous	Exon 4 of 8	NP_001182177.2	Q7Z2E3-7
	APTX	NM_001195249.2		c.318C>T	p.Asn106Asn	synonymous	Exon 4 of 8	NP_001182178.1	Q7Z2E3-7
	APTX	NM_001368995.1		c.318C>T	p.Asn106Asn	synonymous	Exon 4 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.318C>T	p.Asn106Asn	synonymous	Exon 4 of 8	ENSP00000369145.2	Q7Z2E3-7
	APTX	ENST00000379819.6	TSL:1	c.318C>T	p.Asn106Asn	synonymous	Exon 5 of 9	ENSP00000369147.2	Q7Z2E3-7
	APTX	ENST00000463596.6	TSL:1	c.318C>T	p.Asn106Asn	synonymous	Exon 4 of 8	ENSP00000419846.1	Q7Z2E3-7

Frequencies

GnomAD3 genomes AF: 0.00766 AC: 1165 AN: 152122 Hom.: 12 Cov.: 32

Gnomad AFR AF: 0.0269

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00262

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: 0.0000441

Gnomad OTH AF: 0.00384

GnomAD2 exomes AF: 0.00204 AC: 512 AN: 251364 AF XY: 0.00149

Gnomad AFR exome AF: 0.0282

Gnomad AMR exome AF: 0.00110

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000704

Gnomad OTH exome AF: 0.000978

GnomAD4 exome AF: 0.000754 AC: 1102 AN: 1461890 Hom.: 13 Cov.: 31 AF XY: 0.000688 AC XY: 500 AN XY: 727246

African (AFR) AF: 0.0273 AC: 913 AN: 33480

American (AMR) AF: 0.00107 AC: 48 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000104 AC: 9 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.000867 AC: 5 AN: 5768

European-Non Finnish (NFE) AF: 0.0000234 AC: 26 AN: 1112012

Other (OTH) AF: 0.00167 AC: 101 AN: 60394

GnomAD4 genome AF: 0.00767 AC: 1167 AN: 152240 Hom.: 12 Cov.: 32 AF XY: 0.00727 AC XY: 541 AN XY: 74434

African (AFR) AF: 0.0269 AC: 1116 AN: 41518

American (AMR) AF: 0.00261 AC: 40 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68024

Other (OTH) AF: 0.00380 AC: 8 AN: 2108

Alfa AF: 0.00337 Hom.: 5

Bravo AF: 0.00922

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not provided (5)
-	-	2	not specified (2)
-	-	1	Ataxia, early-onset, with oculomotor apraxia and hypoalbuminemia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_noAF	Benign	-0.73
CADD	Benign	5.6
DANN	Uncertain	0.98
PhyloP100		-0.30
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs79254654; hg19: chr9-32987707;