9-127695053-TTGATGATGATGA-T

Position:

• chr9-127695053-TTGATGATGATGA-T

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP3 BP6_Moderate BS2

The ENST00000335223.5(PTRH1):​c.282_293delTCATCATCATCA​(p.His94_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 0.00259 in 671,686 control chromosomes in the GnomAD database, including 6 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0024 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0027 (6 hom.)
• Consequence: PTRH1 ENST00000335223.5 disruptive_inframe_deletion
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.09

Genes affected

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

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]

ACMG classification

Verdict is Benign. Variant got -7 ACMG points.

• BP3: Nonframeshift variant in repetitive region in ENST00000335223.5
• BP6: Variant 9-127695053-TTGATGATGATGA-T is Benign according to our data. Variant chr9-127695053-TTGATGATGATGA-T is described in ClinVar as [Likely_benign]. Clinvar id is 2659509.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTRH1	XM_047422774.1	c.539_550delTCATCATCATCA	p.Ile180_Ile183del	disruptive_inframe_deletion	5/5		XP_047278730.1
PTRH1	XM_047422775.1	c.383_394delTCATCATCATCA	p.Ile128_Ile131del	disruptive_inframe_deletion	4/4		XP_047278731.1
STXBP1	NM_001374314.1	c.*67_*78delATGATGATGATG		3_prime_UTR_variant	19/19		NP_001361243.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTRH1	ENST00000335223.5	c.282_293delTCATCATCATCA	p.His94_His97del	disruptive_inframe_deletion	2/3	1		ENSP00000493136.1
STXBP1	ENST00000636962.2	c.*67_*78delATGATGATGATG		3_prime_UTR_variant	19/19	5		ENSP00000489762.1
STXBP1	ENST00000635950.2	n.*67_*78delATGATGATGATG		non_coding_transcript_exon_variant	19/20	5		ENSP00000490903.1
STXBP1	ENST00000635950.2	n.*67_*78delATGATGATGATG		3_prime_UTR_variant	19/20	5		ENSP00000490903.1

Frequencies

GnomAD3 genomes AF: 0.00240 AC: 354 AN: 147598 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00103

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00197

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000200

Gnomad SAS AF: 0.000443

Gnomad FIN AF: 0.00191

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00391

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00189 AC: 222 AN: 117166 Hom.: 3 AF XY: 0.00185 AC XY: 118 AN XY: 63914

Gnomad AFR exome AF: 0.000735

Gnomad AMR exome AF: 0.000985

Gnomad ASJ exome AF: 0.000135

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000206

Gnomad FIN exome AF: 0.000629

Gnomad NFE exome AF: 0.00391

Gnomad OTH exome AF: 0.00249

GnomAD4 exome AF: 0.00265 AC: 1389 AN: 523968 Hom.: 6 AF XY: 0.00254 AC XY: 719 AN XY: 283484

Gnomad4 AFR exome AF: 0.00140

Gnomad4 AMR exome AF: 0.000733

Gnomad4 ASJ exome AF: 0.000159

Gnomad4 EAS exome AF: 0.0000631

Gnomad4 SAS exome AF: 0.000237

Gnomad4 FIN exome AF: 0.000796

Gnomad4 NFE exome AF: 0.00407

Gnomad4 OTH exome AF: 0.00226

GnomAD4 genome AF: 0.00240 AC: 354 AN: 147718 Hom.: 0 Cov.: 0 AF XY: 0.00228 AC XY: 164 AN XY: 71782

Gnomad4 AFR AF: 0.00103

Gnomad4 AMR AF: 0.00197

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000201

Gnomad4 SAS AF: 0.000443

Gnomad4 FIN AF: 0.00191

Gnomad4 NFE AF: 0.00391

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Oct 01, 2024

PTRH1: BS2 -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs57076743; hg19: chr9-130457332;