19-7629716-C-T

Variant names:

• chr19-7629716-C-T
• rs794085
• ENST00000923270.1:c.-118C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000923270.1(PET100):​c.-118C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000761 in 1,313,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.6e-7 (0 hom.)
• Consequence: PET100 ENST00000923270.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.54
• Publications: 0 publications found

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]

XAB2 (HGNC:14089): (XPA binding protein 2) Involved in mRNA splicing, via spliceosome; transcription, DNA-templated; and transcription-coupled nucleotide-excision repair. Located in nucleoplasm. Part of U2-type catalytic step 2 spliceosome. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000268400 (HGNC:):

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 Gene-Disease associations (from GenCC):

• familial hemophagocytic lymphohistiocytosis 5

  Inheritance: AD, AR Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Ambry Genetics, ClinGen, PanelApp Australia, Labcorp Genetics (formerly Invitae)
• hereditary hemophagocytic lymphohistiocytosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• microvillus inclusion disease

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000923270.1. 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
	XAB2	NM_020196.3	MANE Select	c.-189G>A		upstream_gene	N/A	NP_064581.2	Q9HCS7
	PET100	NM_001171155.2	MANE Select	c.-118C>T		upstream_gene	N/A	NP_001164626.1	P0DJ07
	STXBP2	NM_001414484.1		c.-315C>T		upstream_gene	N/A	NP_001401413.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PET100	ENST00000923270.1		c.-118C>T		5_prime_UTR	Exon 1 of 3	ENSP00000593329.1
	XAB2	ENST00000358368.5	TSL:1 MANE Select	c.-189G>A		upstream_gene	N/A	ENSP00000351137.3	Q9HCS7
	PET100	ENST00000594797.6	TSL:1 MANE Select	c.-118C>T		upstream_gene	N/A	ENSP00000470539.1	P0DJ07

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.61e-7 AC: 1 AN: 1313892 Hom.: 0 Cov.: 20 AF XY: 0.00000154 AC XY: 1 AN XY: 650208

African (AFR) AF: 0.00 AC: 0 AN: 29854

American (AMR) AF: 0.00 AC: 0 AN: 33962

Ashkenazi Jewish (ASJ) AF: 0.0000412 AC: 1 AN: 24276

East Asian (EAS) AF: 0.00 AC: 0 AN: 35164

South Asian (SAS) AF: 0.00 AC: 0 AN: 77162

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5506

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1016024

Other (OTH) AF: 0.00 AC: 0 AN: 55342

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.51
DANN	Benign	0.88
PhyloP100		-1.5
PromoterAI		-0.026	Neutral

Splicing

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

Other links and lift over

dbSNP: rs794085; hg19: chr19-7694602;