Genetic Variant PTRH1:p.His95_His97del (chr9-127695053-TTGATGATGA-T) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP3BS1BS2

The ENST00000335223.5(PTRH1):c.285_293delTCATCATCA(p.His95_His97del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0347 in 671,758 control chromosomes in the GnomAD database, including 366 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.033 ( 90 hom., cov: 0)

Exomes 𝑓: 0.035 ( 276 hom. )

Consequence

PTRH1
ENST00000335223.5 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.09

Variant links:

Genes affected

PTRH1 (HGNC:27039): (peptidyl-tRNA hydrolase 1 homolog) Enables RNA binding activity. [provided by Alliance of Genome Resources, Apr 2022]

PTRH1 links:

STXBP1 (HGNC:11444): (syntaxin binding protein 1) This gene encodes a syntaxin-binding protein. The encoded protein appears to play a role in release of neurotransmitters via regulation of syntaxin, a transmembrane attachment protein receptor. Mutations in this gene have been associated with infantile epileptic encephalopathy-4. Alternatively spliced transcript variants have been described. [provided by RefSeq, Feb 2010]

STXBP1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP3

Nonframeshift variant in repetitive region in ENST00000335223.5

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.033 (4879/147708) while in subpopulation NFE AF= 0.0421 (2820/66938). AF 95% confidence interval is 0.0408. There are 90 homozygotes in gnomad4. There are 2370 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 90 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	Protein
PTRH1	XM_047422774.1 link	c.542_550delTCATCATCA	p.Ile181_Ile183del	disruptive_inframe_deletion	Exon 5 of 5	XP_047278730.1
PTRH1	XM_047422775.1 link	c.386_394delTCATCATCA	p.Ile129_Ile131del	disruptive_inframe_deletion	Exon 4 of 4	XP_047278731.1
STXBP1	NM_001374314.1 link	c.70_78delATGATGATG		3_prime_UTR_variant	Exon 19 of 19	NP_001361243.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	Protein	UniProt
PTRH1	ENST00000335223.5 link	c.285_293delTCATCATCA	p.His95_His97del	disruptive_inframe_deletion	Exon 2 of 3	1	ENSP00000493136.1	A0A286YF52
STXBP1	ENST00000636962.2 link	c.70_78delATGATGATG		3_prime_UTR_variant	Exon 19 of 19	5	ENSP00000489762.1	A0A1B0GWF2
STXBP1	ENST00000635950.2 link	n.70_78delATGATGATG		non_coding_transcript_exon_variant	Exon 19 of 20	5	ENSP00000490903.1	A0A1B0GWF2

Frequencies

GnomAD3 genomes

AF:

0.0331

AC:

4878

AN:

147588

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0204

Gnomad AMI

AF:

0.120

Gnomad AMR

AF:

0.0397

Gnomad ASJ

AF:

0.0189

Gnomad EAS

AF:

0.00441

Gnomad SAS

AF:

0.0330

Gnomad FIN

AF:

0.0245

Gnomad MID

AF:

0.00649

Gnomad NFE

AF:

0.0422

Gnomad OTH

AF:

0.0338

GnomAD3 exomes

AF:

0.0329

AC:

3850

AN:

117166

Hom.:

AF XY:

0.0337

AC XY:

2154

AN XY:

63914

show subpopulations

Gnomad AFR exome

AF:

0.0209

Gnomad AMR exome

AF:

0.0317

Gnomad ASJ exome

AF:

0.0257

Gnomad EAS exome

AF:

0.00317

Gnomad SAS exome

AF:

0.0311

Gnomad FIN exome

AF:

0.0323

Gnomad NFE exome

AF:

0.0431

Gnomad OTH exome

AF:

0.0277

GnomAD4 exome

AF:

0.0352

AC:

18461

AN:

524050

Hom.:

276

AF XY:

0.0354

AC XY:

10043

AN XY:

283516

show subpopulations

Gnomad4 AFR exome

AF:

0.0214

Gnomad4 AMR exome

AF:

0.0311

Gnomad4 ASJ exome

AF:

0.0247

Gnomad4 EAS exome

AF:

0.00221

Gnomad4 SAS exome

AF:

0.0292

Gnomad4 FIN exome

AF:

0.0314

Gnomad4 NFE exome

AF:

0.0426

Gnomad4 OTH exome

AF:

0.0327

GnomAD4 genome

AF:

0.0330

AC:

4879

AN:

147708

Hom.:

Cov.:

AF XY:

0.0330

AC XY:

2370

AN XY:

71778

show subpopulations

Gnomad4 AFR

AF:

0.0204

Gnomad4 AMR

AF:

0.0398

Gnomad4 ASJ

AF:

0.0189

Gnomad4 EAS

AF:

0.00442

Gnomad4 SAS

AF:

0.0330

Gnomad4 FIN

AF:

0.0245

Gnomad4 NFE

AF:

0.0421

Gnomad4 OTH

AF:

0.0334

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over