9-127695053-TTGATGATGATGATGATGATGATGATGATGA-TTGATGATGATGATGATGATGATGATGATGATGATGATGA

Variant names:

Variant summary

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

The ENST00000335223.5(PTRH1):c.285_293dupTCATCATCA(p.His95_His97dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.014 ( 19 hom., cov: 0)

Exomes 𝑓: 0.015 ( 34 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia, G2P
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

new If you want to explore the variant's impact on the transcript ENST00000335223.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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 sas. GnomAdExome4 allele frequency = 0.0146 (7673/524034) while in subpopulation SAS AF = 0.0203 (1200/59124). AF 95% confidence interval is 0.0193. There are 34 homozygotes in GnomAdExome4. There are 4253 alleles in the male GnomAdExome4 subpopulation. Median coverage is 0. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 19 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.70_78dupATGATGATG		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.285_293dupTCATCATCA	p.His95_His97dup	disruptive_inframe_insertion	Exon 2 of 3	ENSP00000493136.1	A0A286YF52
STXBP1	ENST00000636962.2	TSL:5	c.70_78dupATGATGATG		3_prime_UTR	Exon 19 of 19	ENSP00000489762.1	A0A1B0GWF2
STXBP1	ENST00000635950.2	TSL:5	n.70_78dupATGATGATG		non_coding_transcript_exon	Exon 19 of 20	ENSP00000490903.1	A0A1B0GWF2

Frequencies

GnomAD3 genomes

AF:

0.0139

AC:

2051

AN:

147578

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0139

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00776

Gnomad ASJ

AF:

0.00610

Gnomad EAS

AF:

0.0160

Gnomad SAS

AF:

0.0171

Gnomad FIN

AF:

0.0128

Gnomad MID

AF:

0.00974

Gnomad NFE

AF:

0.0156

Gnomad OTH

AF:

0.0149

GnomAD2 exomes

AF:

0.0129

AC:

1510

AN:

117166

AF XY:

0.0128

show subpopulations

Gnomad AFR exome

AF:

0.0143

Gnomad AMR exome

AF:

0.00745

Gnomad ASJ exome

AF:

0.00541

Gnomad EAS exome

AF:

0.0199

Gnomad FIN exome

AF:

0.0130

Gnomad NFE exome

AF:

0.0131

Gnomad OTH exome

AF:

0.0122

GnomAD4 exome

AF:

0.0146

AC:

7673

AN:

524034

Hom.:

Cov.:

AF XY:

0.0150

AC XY:

4253

AN XY:

283506

show subpopulations

African (AFR)

AF:

0.0114

AC:

170

AN:

14962

American (AMR)

AF:

0.00995

AC:

326

AN:

32752

Ashkenazi Jewish (ASJ)

AF:

0.00736

AC:

139

AN:

18874

East Asian (EAS)

AF:

0.0140

AC:

444

AN:

31682

South Asian (SAS)

AF:

0.0203

AC:

1200

AN:

59124

European-Finnish (FIN)

AF:

0.0159

AC:

499

AN:

31420

Middle Eastern (MID)

AF:

0.0105

AC:

AN:

3896

European-Non Finnish (NFE)

AF:

0.0148

AC:

4466

AN:

302158

Other (OTH)

AF:

0.0133

AC:

388

AN:

29166

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

400

800

1199

1599

1999

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

102

136

170

<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:

0.0139

AC:

2051

AN:

147698

Hom.:

Cov.:

AF XY:

0.0137

AC XY:

982

AN XY:

71766

show subpopulations

African (AFR)

AF:

0.0138

AC:

552

AN:

39972

American (AMR)

AF:

0.00768

AC:

113

AN:

14716

Ashkenazi Jewish (ASJ)

AF:

0.00610

AC:

AN:

3444

East Asian (EAS)

AF:

0.0159

AC:

AN:

4980

South Asian (SAS)

AF:

0.0171

AC:

AN:

4510

European-Finnish (FIN)

AF:

0.0128

AC:

127

AN:

9920

Middle Eastern (MID)

AF:

0.00694

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.0156

AC:

1047

AN:

66930

Other (OTH)

AF:

0.0162

AC:

AN:

2038

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

196

293

391

489

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

150

<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:

0.0100

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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