ENST00000335223.5:c.276_293delTCATCATCATCATCATCA

Variant names:

• chr9-127695053-TTGATGATGATGATGATGA-T
• rs57076743
• ENST00000335223.5:c.276_293delTCATCATCATCATCATCA

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP3

The ENST00000335223.5(PTRH1):​c.276_293delTCATCATCATCATCATCA​(p.His92_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 0.0000114 in 524,098 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000011 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PTRH1 ENST00000335223.5 disruptive_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.09
• Publications: 0 publications found

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]

STXBP1 Gene-Disease associations (from GenCC):

• developmental and epileptic encephalopathy, 4

  Inheritance: AD, AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Ambry Genetics, PanelApp Australia, Labcorp Genetics (formerly Invitae)
• genetic developmental and epileptic encephalopathy

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
• atypical Rett syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• autosomal dominant non-syndromic intellectual disability

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Dravet syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• infantile spasms

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• undetermined early-onset epileptic encephalopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• autism spectrum disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• intellectual disability

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP3: Nonframeshift variant in repetitive region in ENST00000335223.5

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000335223.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STXBP1	NM_001374314.1		c.*61_*78delATGATGATGATGATGATG		3_prime_UTR	Exon 19 of 19	NP_001361243.1	A0A1B0GWF2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTRH1	ENST00000335223.5	TSL:1	c.276_293delTCATCATCATCATCATCA	p.His92_His97del	disruptive_inframe_deletion	Exon 2 of 3	ENSP00000493136.1	A0A286YF52
	STXBP1	ENST00000636962.2	TSL:5	c.*61_*78delATGATGATGATGATGATG		3_prime_UTR	Exon 19 of 19	ENSP00000489762.1	A0A1B0GWF2
	STXBP1	ENST00000635950.2	TSL:5	n.*61_*78delATGATGATGATGATGATG		non_coding_transcript_exon	Exon 19 of 20	ENSP00000490903.1	A0A1B0GWF2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 147596 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000114 AC: 6 AN: 524098 Hom.: 0 AF XY: 0.0000212 AC XY: 6 AN XY: 283540

African (AFR) AF: 0.00 AC: 0 AN: 14968

American (AMR) AF: 0.00 AC: 0 AN: 32760

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18876

East Asian (EAS) AF: 0.00 AC: 0 AN: 31682

South Asian (SAS) AF: 0.00 AC: 0 AN: 59136

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31424

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3896

European-Non Finnish (NFE) AF: 0.0000199 AC: 6 AN: 302182

Other (OTH) AF: 0.00 AC: 0 AN: 29174

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 147596 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 71654

African (AFR) AF: 0.00 AC: 0 AN: 39854

American (AMR) AF: 0.00 AC: 0 AN: 14696

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3446

East Asian (EAS) AF: 0.00 AC: 0 AN: 4992

South Asian (SAS) AF: 0.00 AC: 0 AN: 4516

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9922

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 308

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66950

Other (OTH) AF: 0.00 AC: 0 AN: 2012

Alfa AF: 0.00 Hom.: 1157

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs57076743; hg19: chr9-130457332;