9-127695053-TTGATGATGATGATGATGATGATGATGATGA-TTGA

Variant names:

• chr9-127695053-TTGATGATGATGATGATGATGATGATGA-T
• ENST00000335223.5:c.267_293delTCATCATCATCATCATCATCATCATCA

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP3

The ENST00000335223.5(PTRH1):​c.267_293delTCATCATCATCATCATCATCATCATCA​(p.His89_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 0.00000191 in 524,098 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. H89H) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.0000019 (0 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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP3: Nonframeshift variant in repetitive region in ENST00000335223.5

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTRH1	XM_047422774.1	c.524_550delTCATCATCATCATCATCATCATCATCA	p.Ile175_Ile183del	disruptive_inframe_deletion	Exon 5 of 5		XP_047278730.1
PTRH1	XM_047422775.1	c.368_394delTCATCATCATCATCATCATCATCATCA	p.Ile123_Ile131del	disruptive_inframe_deletion	Exon 4 of 4		XP_047278731.1
STXBP1	NM_001374314.1	c.*52_*78delATGATGATGATGATGATGATGATGATG		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.267_293delTCATCATCATCATCATCATCATCATCA	p.His89_His97del	disruptive_inframe_deletion	Exon 2 of 3	1		ENSP00000493136.1
STXBP1	ENST00000636962.2	c.*52_*78delATGATGATGATGATGATGATGATGATG		3_prime_UTR_variant	Exon 19 of 19	5		ENSP00000489762.1
STXBP1	ENST00000635950.2	n.*52_*78delATGATGATGATGATGATGATGATGATG		non_coding_transcript_exon_variant	Exon 19 of 20	5		ENSP00000490903.1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.00000191 AC: 1 AN: 524098 Hom.: 0 AF XY: 0.00000353 AC XY: 1 AN XY: 283540

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000331

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 0

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-130457332;