2-24790654-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001013663.2(PTRHD1):c.253-73C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.49 in 1,445,678 control chromosomes in the GnomAD database, including 177,082 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.42 (15262 hom., cov: 32)
  • Exomes 𝑓: 0.50 (161820 hom.)
• Consequence: PTRHD1 NM_001013663.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.899

Genes affected

PTRHD1 (HGNC:33782): (peptidyl-tRNA hydrolase domain containing 1) This gene encodes the enzyme peptidyl-tRNA hydrolase. Peptidyl-tRNA hydrolases perform the essential function of recycling peptidyl-tRNAs. Mutations in this gene are associated with autosomal-recessive intellectual disability and parkinsonism. [provided by RefSeq, May 2017]

LOC105369164 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 2-24790654-G-C is Benign according to our data. Variant chr2-24790654-G-C is described in ClinVar as [Benign]. Clinvar id is 1221296.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.567 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTRHD1	NM_001013663.2	c.253-73C>G		intron_variant		ENST00000328379.6
LOC105369164	XR_939843.4	n.1636C>G		non_coding_transcript_exon_variant	3/3
LOC105369164	XR_001739341.2	n.868C>G		non_coding_transcript_exon_variant	4/4
LOC105369164	XR_007086245.1	n.1420C>G		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTRHD1	ENST00000328379.6	c.253-73C>G		intron_variant		1	NM_001013663.2	P1

Frequencies

GnomAD3 genomes AF: 0.418 AC: 63499 AN: 151910 Hom.: 15248 Cov.: 32

Gnomad AFR AF: 0.170

Gnomad AMI AF: 0.391

Gnomad AMR AF: 0.576

Gnomad ASJ AF: 0.495

Gnomad EAS AF: 0.562

Gnomad SAS AF: 0.530

Gnomad FIN AF: 0.458

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.504

Gnomad OTH AF: 0.448

GnomAD4 exome AF: 0.498 AC: 644335 AN: 1293650 Hom.: 161820 AF XY: 0.499 AC XY: 318305 AN XY: 638474

Gnomad4 AFR exome AF: 0.154

Gnomad4 AMR exome AF: 0.641

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.509

Gnomad4 SAS exome AF: 0.516

Gnomad4 FIN exome AF: 0.467

Gnomad4 NFE exome AF: 0.504

Gnomad4 OTH exome AF: 0.494

GnomAD4 genome AF: 0.418 AC: 63508 AN: 152028 Hom.: 15262 Cov.: 32 AF XY: 0.422 AC XY: 31326 AN XY: 74280

Gnomad4 AFR AF: 0.169

Gnomad4 AMR AF: 0.577

Gnomad4 ASJ AF: 0.495

Gnomad4 EAS AF: 0.562

Gnomad4 SAS AF: 0.528

Gnomad4 FIN AF: 0.458

Gnomad4 NFE AF: 0.504

Gnomad4 OTH AF: 0.454

Alfa AF: 0.308 Hom.: 861

Bravo AF: 0.415

Asia WGS AF: 0.564 AC: 1958 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 14, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.31
Dann	Benign	0.38

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

Publications

LitVar

Other links and lift over

dbSNP: rs12471620; hg19: chr2-25013523; COSMIC: COSV53232185; COSMIC: COSV53232185;