Genetic Variant PTRH1:p.His97del (chr9-127695053-TTGA-T) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP3BA1

The ENST00000335223.5(PTRH1):c.291_293delTCA(p.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 0.0138 in 663,192 control chromosomes in the GnomAD database, including 360 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.036 ( 279 hom., cov: 0)

Exomes 𝑓: 0.0074 ( 81 hom. )

Consequence

PTRH1
ENST00000335223.5 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.549

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

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.

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.76_78delATG		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.291_293delTCA	p.His97del	disruptive_inframe_deletion	Exon 2 of 3	ENSP00000493136.1	A0A286YF52
STXBP1	ENST00000636962.2	TSL:5	c.76_78delATG		3_prime_UTR	Exon 19 of 19	ENSP00000489762.1	A0A1B0GWF2
STXBP1	ENST00000635950.2	TSL:5	n.76_78delATG		non_coding_transcript_exon	Exon 19 of 20	ENSP00000490903.1	A0A1B0GWF2

Frequencies

GnomAD3 genomes

AF:

0.0363

AC:

5356

AN:

147570

Hom.:

279

Cov.:

show subpopulations

Gnomad AFR

AF:

0.120

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0233

Gnomad ASJ

AF:

0.000580

Gnomad EAS

AF:

0.00341

Gnomad SAS

AF:

0.00443

Gnomad FIN

AF:

0.000403

Gnomad MID

AF:

0.0130

Gnomad NFE

AF:

0.00239

Gnomad OTH

AF:

0.0224

GnomAD2 exomes

AF:

0.0126

AC:

1478

AN:

117166

AF XY:

0.0108

show subpopulations

Gnomad AFR exome

AF:

0.145

Gnomad AMR exome

AF:

0.0119

Gnomad ASJ exome

AF:

0.00257

Gnomad EAS exome

AF:

0.00876

Gnomad FIN exome

AF:

0.00168

Gnomad NFE exome

AF:

0.00430

Gnomad OTH exome

AF:

0.00776

GnomAD4 exome

AF:

0.00737

AC:

3798

AN:

515502

Hom.:

AF XY:

0.00659

AC XY:

1840

AN XY:

279194

show subpopulations

African (AFR)

AF:

0.115

AC:

1710

AN:

14918

American (AMR)

AF:

0.0130

AC:

421

AN:

32364

Ashkenazi Jewish (ASJ)

AF:

0.00150

AC:

AN:

18614

East Asian (EAS)

AF:

0.00729

AC:

221

AN:

30296

South Asian (SAS)

AF:

0.00426

AC:

249

AN:

58432

European-Finnish (FIN)

AF:

0.00106

AC:

AN:

31134

Middle Eastern (MID)

AF:

0.00751

AC:

AN:

3860

European-Non Finnish (NFE)

AF:

0.00256

AC:

760

AN:

297186

Other (OTH)

AF:

0.0121

AC:

347

AN:

28698

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

169

337

506

674

843

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

128

160

<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:

0.0364

AC:

5374

AN:

147690

Hom.:

279

Cov.:

AF XY:

0.0354

AC XY:

2538

AN XY:

71766

show subpopulations

African (AFR)

AF:

0.120

AC:

4781

AN:

39948

American (AMR)

AF:

0.0232

AC:

342

AN:

14718

Ashkenazi Jewish (ASJ)

AF:

0.000580

AC:

AN:

3446

East Asian (EAS)

AF:

0.00341

AC:

AN:

4980

South Asian (SAS)

AF:

0.00421

AC:

AN:

4510

European-Finnish (FIN)

AF:

0.000403

AC:

AN:

9920

Middle Eastern (MID)

AF:

0.0139

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.00239

AC:

160

AN:

66942

Other (OTH)

AF:

0.0221

AC:

AN:

2038

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

227

454

681

908

1135

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

156

208

260

<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:

0.00776

Hom.:

1157

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.55

Splicing

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

Publications

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9-127695053-TTGATGATGATGATGATGATGATGATGATGA-TTGATGATGATGATGATGATGATGATGA

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