chr9-127695053-T-TTGATGATGATGA

Variant names:

• chr9-127695053-T-TTGATGATGATGA
• rs57076743
• ENST00000335223.5:c.282_293dupTCATCATCATCA

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP3 BS1 BS2

The ENST00000335223.5(PTRH1):​c.282_293dupTCATCATCATCA​(p.His94_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 0.0068 (18 hom., cov: 0)
  • Exomes 𝑓: 0.0018 (2 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
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00682 (1007/147712) while in subpopulation AFR AF= 0.022 (879/39968). AF 95% confidence interval is 0.0208. There are 18 homozygotes in gnomad4. There are 446 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 18 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTRH1	XM_047422774.1	c.539_550dupTCATCATCATCA	p.Ile180_Ile183dup	conservative_inframe_insertion	Exon 5 of 5		XP_047278730.1
PTRH1	XM_047422775.1	c.383_394dupTCATCATCATCA	p.Ile128_Ile131dup	conservative_inframe_insertion	Exon 4 of 4		XP_047278731.1
STXBP1	NM_001374314.1	c.*67_*78dupATGATGATGATG		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.282_293dupTCATCATCATCA	p.His94_His97dup	disruptive_inframe_insertion	Exon 2 of 3	1		ENSP00000493136.1
STXBP1	ENST00000636962.2	c.*67_*78dupATGATGATGATG		3_prime_UTR_variant	Exon 19 of 19	5		ENSP00000489762.1
STXBP1	ENST00000635950.2	n.*67_*78dupATGATGATGATG		non_coding_transcript_exon_variant	Exon 19 of 20	5		ENSP00000490903.1

Frequencies

GnomAD3 genomes AF: 0.00680 AC: 1003 AN: 147592 Hom.: 18 Cov.: 0

Gnomad AFR AF: 0.0220

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00313

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00140

Gnomad SAS AF: 0.00177

Gnomad FIN AF: 0.000101

Gnomad MID AF: 0.00325

Gnomad NFE AF: 0.000732

Gnomad OTH AF: 0.00795

GnomAD4 exome AF: 0.00179 AC: 937 AN: 524090 Hom.: 2 Cov.: 0 AF XY: 0.00169 AC XY: 478 AN XY: 283536

Gnomad4 AFR exome AF: 0.0223

Gnomad4 AMR exome AF: 0.00156

Gnomad4 ASJ exome AF: 0.000318

Gnomad4 EAS exome AF: 0.00297

Gnomad4 SAS exome AF: 0.00238

Gnomad4 FIN exome AF: 0.000159

Gnomad4 NFE exome AF: 0.000688

Gnomad4 OTH exome AF: 0.00302

GnomAD4 genome AF: 0.00682 AC: 1007 AN: 147712 Hom.: 18 Cov.: 0 AF XY: 0.00621 AC XY: 446 AN XY: 71780

Gnomad4 AFR AF: 0.0220

Gnomad4 AMR AF: 0.00313

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00141

Gnomad4 SAS AF: 0.00177

Gnomad4 FIN AF: 0.000101

Gnomad4 NFE AF: 0.000732

Gnomad4 OTH AF: 0.00785

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;