9-127695053-TTGATGATGATGATGATGATGATGATGATGA-TTGATGATGATGATGATGATGATGATGATGATGATGA

Variant names:

• chr9-127695053-T-TTGATGA
• rs57076743
• ENST00000335223.5:c.288_293dupTCATCA

Variant summary

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

The ENST00000335223.5(PTRH1):​c.288_293dupTCATCA​(p.His96_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 0.084 (588 hom., cov: 0)
  • Exomes 𝑓: 0.076 (761 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 (SAS) allele frequency at 95% confidence interval = 0.128 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTRH1	XM_047422774.1	c.545_550dupTCATCA	p.Ile182_Ile183dup	conservative_inframe_insertion	Exon 5 of 5		XP_047278730.1
PTRH1	XM_047422775.1	c.389_394dupTCATCA	p.Ile130_Ile131dup	conservative_inframe_insertion	Exon 4 of 4		XP_047278731.1
STXBP1	NM_001374314.1	c.*73_*78dupATGATG		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.288_293dupTCATCA	p.His96_His97dup	disruptive_inframe_insertion	Exon 2 of 3	1		ENSP00000493136.1
STXBP1	ENST00000636962.2	c.*73_*78dupATGATG		3_prime_UTR_variant	Exon 19 of 19	5		ENSP00000489762.1
STXBP1	ENST00000635950.2	n.*73_*78dupATGATG		non_coding_transcript_exon_variant	Exon 19 of 20	5		ENSP00000490903.1

Frequencies

GnomAD3 genomes AF: 0.0837 AC: 12344 AN: 147494 Hom.: 587 Cov.: 0

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.00667

Gnomad AMR AF: 0.0731

Gnomad ASJ AF: 0.0461

Gnomad EAS AF: 0.0852

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.0638

Gnomad MID AF: 0.0784

Gnomad NFE AF: 0.0648

Gnomad OTH AF: 0.0820

GnomAD3 exomes AF: 0.0746 AC: 8741 AN: 117166 Hom.: 214 AF XY: 0.0746 AC XY: 4768 AN XY: 63914

Gnomad AFR exome AF: 0.133

Gnomad AMR exome AF: 0.0759

Gnomad ASJ exome AF: 0.0392

Gnomad EAS exome AF: 0.0910

Gnomad SAS exome AF: 0.108

Gnomad FIN exome AF: 0.0593

Gnomad NFE exome AF: 0.0572

Gnomad OTH exome AF: 0.0709

GnomAD4 exome AF: 0.0759 AC: 39714 AN: 523304 Hom.: 761 Cov.: 0 AF XY: 0.0784 AC XY: 22196 AN XY: 283070

Gnomad4 AFR exome AF: 0.125

Gnomad4 AMR exome AF: 0.0808

Gnomad4 ASJ exome AF: 0.0456

Gnomad4 EAS exome AF: 0.0835

Gnomad4 SAS exome AF: 0.124

Gnomad4 FIN exome AF: 0.0720

Gnomad4 NFE exome AF: 0.0653

Gnomad4 OTH exome AF: 0.0755

GnomAD4 genome AF: 0.0837 AC: 12361 AN: 147614 Hom.: 588 Cov.: 0 AF XY: 0.0852 AC XY: 6113 AN XY: 71710

Gnomad4 AFR AF: 0.123

Gnomad4 AMR AF: 0.0731

Gnomad4 ASJ AF: 0.0461

Gnomad4 EAS AF: 0.0854

Gnomad4 SAS AF: 0.137

Gnomad4 FIN AF: 0.0638

Gnomad4 NFE AF: 0.0648

Gnomad4 OTH AF: 0.0849

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;