Variant 19-7630450-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001171155.2(PET100):c.28-123A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.345 in 743,570 control chromosomes in the GnomAD database, including 45,640 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.33 ( 8559 hom., cov: 31)

Exomes 𝑓: 0.35 ( 37081 hom. )

Consequence

PET100
NM_001171155.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.00500

Variant links:

Genes affected

PET100 (HGNC:40038): (PET100 cytochrome c oxidase chaperone) Mitochondrial complex IV, or cytochrome c oxidase, is a large transmembrane protein complex that is part of the respiratory electron transport chain of mitochondria. The small protein encoded by this gene plays a role in the biogenesis of mitochondrial complex IV. This protein localizes to the inner mitochondrial membrane and is exposed to the intermembrane space. Mutations in this gene are associated with mitochondrial complex IV deficiency. This gene has a pseudogene on chromosome 3. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2014]

PET100 links:

ENSG00000268400 (HGNC:):

ENSG00000268400 links:

STXBP2 (HGNC:11445): (syntaxin binding protein 2) This gene encodes a member of the STXBP/unc-18/SEC1 family. The encoded protein is involved in intracellular trafficking, control of SNARE (soluble NSF attachment protein receptor) complex assembly, and the release of cytotoxic granules by natural killer cells. Mutations in this gene are associated with familial hemophagocytic lymphohistiocytosis. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene. [provided by RefSeq, Jan 2013]

STXBP2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BP6

Variant 19-7630450-A-G is Benign according to our data. Variant chr19-7630450-A-G is described in ClinVar as [Benign]. Clinvar id is 1274441.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.362 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
PET100	NM_001171155.2 linkuse as main transcript	c.28-123A>G	intron_variant	ENST00000594797.6	NP_001164626.1	P0DJ07
STXBP2	NM_001414484.1 linkuse as main transcript	c.-170-123A>G	intron_variant		NP_001401413.1
PET100	NR_033242.2 linkuse as main transcript	n.69-123A>G	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PET100	ENST00000594797.6 linkuse as main transcript	c.28-123A>G		intron_variant		1	NM_001171155.2	ENSP00000470539.1		P0DJ07
ENSG00000268400	ENST00000698368.1 linkuse as main transcript	n.28-123A>G		intron_variant				ENSP00000513686.1		A0A8V8TM65

Frequencies

GnomAD3 genomes

AF:

0.331

AC:

50216

AN:

151668

Hom.:

8552

Cov.:

show subpopulations

Gnomad AFR

AF:

0.252

Gnomad AMI

AF:

0.208

Gnomad AMR

AF:

0.368

Gnomad ASJ

AF:

0.292

Gnomad EAS

AF:

0.221

Gnomad SAS

AF:

0.298

Gnomad FIN

AF:

0.454

Gnomad MID

AF:

0.321

Gnomad NFE

AF:

0.366

Gnomad OTH

AF:

0.338

GnomAD4 exome

AF:

0.349

AC:

206381

AN:

591784

Hom.:

37081

Cov.:

AF XY:

0.347

AC XY:

108560

AN XY:

312912

show subpopulations

Gnomad4 AFR exome

AF:

0.254

Gnomad4 AMR exome

AF:

0.365

Gnomad4 ASJ exome

AF:

0.290

Gnomad4 EAS exome

AF:

0.212

Gnomad4 SAS exome

AF:

0.298

Gnomad4 FIN exome

AF:

0.433

Gnomad4 NFE exome

AF:

0.367

Gnomad4 OTH exome

AF:

0.347

GnomAD4 genome

AF:

0.331

AC:

50245

AN:

151786

Hom.:

8559

Cov.:

AF XY:

0.334

AC XY:

24774

AN XY:

74170

show subpopulations

Gnomad4 AFR

AF:

0.252

Gnomad4 AMR

AF:

0.368

Gnomad4 ASJ

AF:

0.292

Gnomad4 EAS

AF:

0.221

Gnomad4 SAS

AF:

0.298

Gnomad4 FIN

AF:

0.454

Gnomad4 NFE

AF:

0.366

Gnomad4 OTH

AF:

0.342

Alfa

AF:

0.342

Hom.:

1676

Bravo

AF:

0.319

Asia WGS

AF:

0.279

AC:

973

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 23, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

DANN

Benign

0.70

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over