chr9-127695053-T-TTGA

Variant names:

• chr9-127695053-T-TTGA
• rs57076743
• ENST00000335223.5:c.291_293dupTCA

Variant summary

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

The ENST00000335223.5(PTRH1):​c.291_293dupTCA​(p.His97dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.46 (15953 hom., cov: 0)
  • Exomes 𝑓: 0.39 (24430 hom.)
• Consequence: PTRH1 ENST00000335223.5 disruptive_inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.463

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 (AMR) allele frequency at 95% confidence interval = 0.46 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTRH1	XM_047422774.1	c.548_550dupTCA	p.Ile183dup	conservative_inframe_insertion	Exon 5 of 5		XP_047278730.1
PTRH1	XM_047422775.1	c.392_394dupTCA	p.Ile131dup	conservative_inframe_insertion	Exon 4 of 4		XP_047278731.1
STXBP1	NM_001374314.1	c.*76_*78dupATG		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_293dupTCA	p.His97dup	disruptive_inframe_insertion	Exon 2 of 3	1		ENSP00000493136.1
STXBP1	ENST00000636962.2	c.*76_*78dupATG		3_prime_UTR_variant	Exon 19 of 19	5		ENSP00000489762.1
STXBP1	ENST00000635950.2	n.*76_*78dupATG		non_coding_transcript_exon_variant	Exon 19 of 20	5		ENSP00000490903.1

Frequencies

GnomAD3 genomes AF: 0.462 AC: 68049 AN: 147420 Hom.: 15943 Cov.: 0

Gnomad AFR AF: 0.451

Gnomad AMI AF: 0.267

Gnomad AMR AF: 0.464

Gnomad ASJ AF: 0.512

Gnomad EAS AF: 0.249

Gnomad SAS AF: 0.453

Gnomad FIN AF: 0.590

Gnomad MID AF: 0.539

Gnomad NFE AF: 0.464

Gnomad OTH AF: 0.476

GnomAD3 exomes AF: 0.386 AC: 45210 AN: 117166 Hom.: 4557 AF XY: 0.384 AC XY: 24569 AN XY: 63914

Gnomad AFR exome AF: 0.402

Gnomad AMR exome AF: 0.396

Gnomad ASJ exome AF: 0.415

Gnomad EAS exome AF: 0.255

Gnomad SAS exome AF: 0.390

Gnomad FIN exome AF: 0.459

Gnomad NFE exome AF: 0.390

Gnomad OTH exome AF: 0.402

GnomAD4 exome AF: 0.388 AC: 202829 AN: 522098 Hom.: 24430 Cov.: 0 AF XY: 0.388 AC XY: 109439 AN XY: 282348

Gnomad4 AFR exome AF: 0.384

Gnomad4 AMR exome AF: 0.375

Gnomad4 ASJ exome AF: 0.410

Gnomad4 EAS exome AF: 0.216

Gnomad4 SAS exome AF: 0.380

Gnomad4 FIN exome AF: 0.487

Gnomad4 NFE exome AF: 0.397

Gnomad4 OTH exome AF: 0.393

GnomAD4 genome AF: 0.462 AC: 68093 AN: 147540 Hom.: 15953 Cov.: 0 AF XY: 0.466 AC XY: 33388 AN XY: 71690

Gnomad4 AFR AF: 0.451

Gnomad4 AMR AF: 0.464

Gnomad4 ASJ AF: 0.512

Gnomad4 EAS AF: 0.249

Gnomad4 SAS AF: 0.451

Gnomad4 FIN AF: 0.590

Gnomad4 NFE AF: 0.464

Gnomad4 OTH AF: 0.474

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;