ENST00000335223.5:c.288_293delTCATCA

Variant names:

• chr9-127695053-TTGATGA-T
• rs57076743
• ENST00000335223.5:c.288_293delTCATCA

Variant summary

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

The ENST00000335223.5(PTRH1):​c.288_293delTCATCA​(p.His96_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 0.00233 in 671,734 control chromosomes in the GnomAD database, including 15 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0058 (10 hom., cov: 0)
  • Exomes 𝑓: 0.0013 (5 hom.)
• Consequence: PTRH1 ENST00000335223.5 disruptive_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• 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 -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 = 0.00585 (864/147716) while in subpopulation AFR AF= 0.0198 (790/39972). AF 95% confidence interval is 0.0186. There are 10 homozygotes in gnomad4. There are 415 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTRH1	XM_047422774.1	c.545_550delTCATCA	p.Ile182_Ile183del	disruptive_inframe_deletion	Exon 5 of 5		XP_047278730.1
PTRH1	XM_047422775.1	c.389_394delTCATCA	p.Ile130_Ile131del	disruptive_inframe_deletion	Exon 4 of 4		XP_047278731.1
STXBP1	NM_001374314.1	c.*73_*78delATGATG		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_293delTCATCA	p.His96_His97del	disruptive_inframe_deletion	Exon 2 of 3	1		ENSP00000493136.1
STXBP1	ENST00000636962.2	c.*73_*78delATGATG		3_prime_UTR_variant	Exon 19 of 19	5		ENSP00000489762.1
STXBP1	ENST00000635950.2	n.*73_*78delATGATG		non_coding_transcript_exon_variant	Exon 19 of 20	5		ENSP00000490903.1

Frequencies

GnomAD3 genomes AF: 0.00581 AC: 857 AN: 147596 Hom.: 8 Cov.: 0

Gnomad AFR AF: 0.0196

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00279

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00200

Gnomad SAS AF: 0.000664

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000254

Gnomad OTH AF: 0.00149

GnomAD4 exome AF: 0.00133 AC: 699 AN: 524018 Hom.: 5 AF XY: 0.00114 AC XY: 323 AN XY: 283504

Gnomad4 AFR exome AF: 0.0202

Gnomad4 AMR exome AF: 0.00180

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00410

Gnomad4 SAS exome AF: 0.000879

Gnomad4 FIN exome AF: 0.0000636

Gnomad4 NFE exome AF: 0.000288

Gnomad4 OTH exome AF: 0.00209

GnomAD4 genome AF: 0.00585 AC: 864 AN: 147716 Hom.: 10 Cov.: 0 AF XY: 0.00578 AC XY: 415 AN XY: 71780

Gnomad4 AFR AF: 0.0198

Gnomad4 AMR AF: 0.00279

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00201

Gnomad4 SAS AF: 0.000665

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000254

Gnomad4 OTH AF: 0.00147

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;