chr9-32973357-C-T

Variant names:

• chr9-32973357-C-T
• rs148292963
• NM_001195248.2:c.*141G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001195248.2(APTX):​c.*141G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00102 in 995,456 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0041 (6 hom., cov: 32)
  • Exomes 𝑓: 0.00046 (1 hom.)
• Consequence: APTX NM_001195248.2 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.315
• Publications: 0 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 9-32973357-C-T is Benign according to our data. Variant chr9-32973357-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 915132.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00411 (626/152234) while in subpopulation AFR AF = 0.0144 (598/41534). AF 95% confidence interval is 0.0134. There are 6 homozygotes in GnomAd4. There are 290 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 6 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.*141G>A		3_prime_UTR	Exon 8 of 8	NP_001182177.2	Q7Z2E3-7
	APTX	NM_001195249.2		c.*141G>A		3_prime_UTR	Exon 8 of 8	NP_001182178.1	Q7Z2E3-7
	APTX	NM_001368995.1		c.*141G>A		3_prime_UTR	Exon 8 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.*141G>A		3_prime_UTR	Exon 8 of 8	ENSP00000369145.2	Q7Z2E3-7
	APTX	ENST00000379819.6	TSL:1	c.*141G>A		3_prime_UTR	Exon 9 of 9	ENSP00000369147.2	Q7Z2E3-7
	APTX	ENST00000309615.8	TSL:1	c.*141G>A		3_prime_UTR	Exon 7 of 7	ENSP00000311547.4	Q7Z2E3-5

Frequencies

GnomAD3 genomes AF: 0.00411 AC: 625 AN: 152116 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.0144

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00137

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: 0.0000294

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.000995 AC: 182 AN: 182884 AF XY: 0.000729

Gnomad AFR exome AF: 0.0153

Gnomad AMR exome AF: 0.000601

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000509

Gnomad OTH exome AF: 0.000400

GnomAD4 exome AF: 0.000458 AC: 386 AN: 843222 Hom.: 1 Cov.: 12 AF XY: 0.000381 AC XY: 168 AN XY: 440706

African (AFR) AF: 0.0140 AC: 297 AN: 21212

American (AMR) AF: 0.000600 AC: 23 AN: 38330

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21966

East Asian (EAS) AF: 0.00 AC: 0 AN: 34872

South Asian (SAS) AF: 0.0000427 AC: 3 AN: 70338

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39232

Middle Eastern (MID) AF: 0.000330 AC: 1 AN: 3032

European-Non Finnish (NFE) AF: 0.0000331 AC: 19 AN: 573854

Other (OTH) AF: 0.00106 AC: 43 AN: 40386

GnomAD4 genome AF: 0.00411 AC: 626 AN: 152234 Hom.: 6 Cov.: 32 AF XY: 0.00390 AC XY: 290 AN XY: 74428

African (AFR) AF: 0.0144 AC: 598 AN: 41534

American (AMR) AF: 0.00137 AC: 21 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

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: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68018

Other (OTH) AF: 0.00237 AC: 5 AN: 2110

Alfa AF: 0.00231 Hom.: 0

Bravo AF: 0.00507

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.4
DANN	Benign	0.50
PhyloP100		-0.32
Mutation Taster		=100/0	polymorphism

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: rs148292963; hg19: chr9-32973355;