9-127695053-TTGATGATGATGATGATGATGATGATGATGA-T

Variant names:

• chr9-127695053-TTGATGATGATGATGATGATGATGATGATGA-T
• rs57076743
• ENST00000335223.5:c.264_293delTCATCATCATCATCATCATCATCATCATCA

Variant summary

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

The ENST00000335223.5(PTRH1):​c.264_293delTCATCATCATCATCATCATCATCATCATCA​(p.His88_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 0.0000119 in 671,696 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000014 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000011 (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.521_550delTCATCATCATCATCATCATCATCATCATCA	p.Ile174_Ile183del	disruptive_inframe_deletion	Exon 5 of 5		XP_047278730.1
PTRH1	XM_047422775.1	c.365_394delTCATCATCATCATCATCATCATCATCATCA	p.Ile122_Ile131del	disruptive_inframe_deletion	Exon 4 of 4		XP_047278731.1
STXBP1	NM_001374314.1	c.*49_*78delATGATGATGATGATGATGATGATGATGATG		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.264_293delTCATCATCATCATCATCATCATCATCATCA	p.His88_His97del	disruptive_inframe_deletion	Exon 2 of 3	1		ENSP00000493136.1
STXBP1	ENST00000636962.2	c.*49_*78delATGATGATGATGATGATGATGATGATGATG		3_prime_UTR_variant	Exon 19 of 19	5		ENSP00000489762.1
STXBP1	ENST00000635950.2	n.*49_*78delATGATGATGATGATGATGATGATGATGATG		non_coding_transcript_exon_variant	Exon 19 of 20	5		ENSP00000490903.1

Frequencies

GnomAD3 genomes AF: 0.0000136 AC: 2 AN: 147598 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000251

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000149

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000114 AC: 6 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: 0.0000199

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000136 AC: 2 AN: 147598 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 71656

Gnomad4 AFR AF: 0.0000251

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000149

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000264

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;