9-127695053-TTGATGATGATGATGATGATGATGATGATGA-TTGATGATGATGATGATGATGATGATGA

Variant names:

• chr9-127695053-TTGA-T
• rs57076743
• ENST00000335223.5:c.291_293delTCA

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP3 BA1

The ENST00000335223.5(PTRH1):​c.291_293delTCA​(p.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 0.0138 in 663,192 control chromosomes in the GnomAD database, including 360 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.036 (279 hom., cov: 0)
  • Exomes 𝑓: 0.0074 (81 hom.)
• Consequence: PTRH1 ENST00000335223.5 disruptive_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.549

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 -9 ACMG points.

• BP3: Nonframeshift variant in repetitive region in ENST00000335223.5
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTRH1	XM_047422774.1	c.548_550delTCA	p.Ile183del	disruptive_inframe_deletion	Exon 5 of 5		XP_047278730.1
PTRH1	XM_047422775.1	c.392_394delTCA	p.Ile131del	disruptive_inframe_deletion	Exon 4 of 4		XP_047278731.1
STXBP1	NM_001374314.1	c.*76_*78delATG		3_prime_UTR_variant	Exon 19 of 19		NP_001361243.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTRH1	ENST00000335223.5	c.291_293delTCA	p.His97del	disruptive_inframe_deletion	Exon 2 of 3	1		ENSP00000493136.1
STXBP1	ENST00000636962.2	c.*76_*78delATG		3_prime_UTR_variant	Exon 19 of 19	5		ENSP00000489762.1
STXBP1	ENST00000635950.2	n.*76_*78delATG		non_coding_transcript_exon_variant	Exon 19 of 20	5		ENSP00000490903.1

Frequencies

GnomAD3 genomes AF: 0.0363 AC: 5356 AN: 147570 Hom.: 279 Cov.: 0

Gnomad AFR AF: 0.120

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0233

Gnomad ASJ AF: 0.000580

Gnomad EAS AF: 0.00341

Gnomad SAS AF: 0.00443

Gnomad FIN AF: 0.000403

Gnomad MID AF: 0.0130

Gnomad NFE AF: 0.00239

Gnomad OTH AF: 0.0224

GnomAD3 exomes AF: 0.0126 AC: 1478 AN: 117166 Hom.: 87 AF XY: 0.0108 AC XY: 692 AN XY: 63914

Gnomad AFR exome AF: 0.145

Gnomad AMR exome AF: 0.0119

Gnomad ASJ exome AF: 0.00257

Gnomad EAS exome AF: 0.00876

Gnomad SAS exome AF: 0.00535

Gnomad FIN exome AF: 0.00168

Gnomad NFE exome AF: 0.00430

Gnomad OTH exome AF: 0.00776

GnomAD4 exome AF: 0.00737 AC: 3798 AN: 515502 Hom.: 81 AF XY: 0.00659 AC XY: 1840 AN XY: 279194

Gnomad4 AFR exome AF: 0.115

Gnomad4 AMR exome AF: 0.0130

Gnomad4 ASJ exome AF: 0.00150

Gnomad4 EAS exome AF: 0.00729

Gnomad4 SAS exome AF: 0.00426

Gnomad4 FIN exome AF: 0.00106

Gnomad4 NFE exome AF: 0.00256

Gnomad4 OTH exome AF: 0.0121

GnomAD4 genome AF: 0.0364 AC: 5374 AN: 147690 Hom.: 279 Cov.: 0 AF XY: 0.0354 AC XY: 2538 AN XY: 71766

Gnomad4 AFR AF: 0.120

Gnomad4 AMR AF: 0.0232

Gnomad4 ASJ AF: 0.000580

Gnomad4 EAS AF: 0.00341

Gnomad4 SAS AF: 0.00421

Gnomad4 FIN AF: 0.000403

Gnomad4 NFE AF: 0.00239

Gnomad4 OTH AF: 0.0221

ClinVar

Not reported in ClinVar

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;