9-127695053-TTGATGATGATGATGATGATGATGATGATGA-TTGATGATGATGATGATGATGATGATGATGATGATGATGATGA

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP3BS1BS2

The ENST00000335223.5(PTRH1):c.282_293dupTCATCATCATCA(p.His94_His97dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_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 0.0068 ( 18 hom., cov: 0)

Exomes 𝑓: 0.0018 ( 2 hom. )

Consequence

PTRH1
ENST00000335223.5 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.463

Publications

0 publications found

Variant links:

Genes affected

PTRH1 (HGNC:27039): (peptidyl-tRNA hydrolase 1 homolog) Enables RNA binding activity. [provided by Alliance of Genome Resources, Apr 2022]

PTRH1 links:

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

STXBP1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 = 0.00682 (1007/147712) while in subpopulation AFR AF = 0.022 (879/39968). AF 95% confidence interval is 0.0208. There are 18 homozygotes in GnomAd4. There are 446 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 18 AR gene

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.67_78dupATGATGATGATG		3_prime_UTR	Exon 19 of 19	NP_001361243.1	A0A1B0GWF2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PTRH1	ENST00000335223.5	TSL:1	c.282_293dupTCATCATCATCA	p.His94_His97dup	disruptive_inframe_insertion	Exon 2 of 3	ENSP00000493136.1	A0A286YF52
STXBP1	ENST00000636962.2	TSL:5	c.67_78dupATGATGATGATG		3_prime_UTR	Exon 19 of 19	ENSP00000489762.1	A0A1B0GWF2
STXBP1	ENST00000635950.2	TSL:5	n.67_78dupATGATGATGATG		non_coding_transcript_exon	Exon 19 of 20	ENSP00000490903.1	A0A1B0GWF2

Frequencies

GnomAD3 genomes

AF:

0.00680

AC:

1003

AN:

147592

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0220

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00313

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00140

Gnomad SAS

AF:

0.00177

Gnomad FIN

AF:

0.000101

Gnomad MID

AF:

0.00325

Gnomad NFE

AF:

0.000732

Gnomad OTH

AF:

0.00795

GnomAD4 exome

AF:

0.00179

AC:

937

AN:

524090

Hom.:

Cov.:

AF XY:

0.00169

AC XY:

478

AN XY:

283536

show subpopulations

African (AFR)

AF:

0.0223

AC:

334

AN:

14968

American (AMR)

AF:

0.00156

AC:

AN:

32758

Ashkenazi Jewish (ASJ)

AF:

0.000318

AC:

AN:

18876

East Asian (EAS)

AF:

0.00297

AC:

AN:

31680

South Asian (SAS)

AF:

0.00238

AC:

141

AN:

59136

European-Finnish (FIN)

AF:

0.000159

AC:

AN:

31424

Middle Eastern (MID)

AF:

0.00257

AC:

AN:

3896

European-Non Finnish (NFE)

AF:

0.000688

AC:

208

AN:

302178

Other (OTH)

AF:

0.00302

AC:

AN:

29174

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.448

Heterozygous variant carriers

148

197

246

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00682

AC:

1007

AN:

147712

Hom.:

Cov.:

AF XY:

0.00621

AC XY:

446

AN XY:

71780

show subpopulations

African (AFR)

AF:

0.0220

AC:

879

AN:

39968

American (AMR)

AF:

0.00313

AC:

AN:

14718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3446

East Asian (EAS)

AF:

0.00141

AC:

AN:

4980

South Asian (SAS)

AF:

0.00177

AC:

AN:

4510

European-Finnish (FIN)

AF:

0.000101

AC:

AN:

9922

Middle Eastern (MID)

AF:

0.00347

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.000732

AC:

AN:

66942

Other (OTH)

AF:

0.00785

AC:

AN:

2038

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

124

165

206

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

1157

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.46

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over