rs794085

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr19-7629716-C-G
• chr19-7629716-C-A
• chr19-7629716-C-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000923270.1(PET100):​c.-118C>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 1,464,596 control chromosomes in the GnomAD database, including 37,448 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.19 (3015 hom., cov: 32)
  • Exomes 𝑓: 0.22 (34433 hom.)
• Consequence: PET100 ENST00000923270.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.54
• Publications: 9 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 19-7629716-C-G is Benign according to our data. Variant chr19-7629716-C-G is described in ClinVar as Benign. ClinVar VariationId is 1270843.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.225 is higher than 0.05.

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>C		upstream_gene	N/A	NP_064581.2	Q9HCS7
	PET100	NM_001171155.2	MANE Select	c.-118C>G		upstream_gene	N/A	NP_001164626.1	P0DJ07
	STXBP2	NM_001414484.1		c.-315C>G		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>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 3	ENSP00000593329.1
	PET100	ENST00000923270.1		c.-118C>G		5_prime_UTR	Exon 1 of 3	ENSP00000593329.1
	XAB2	ENST00000358368.5	TSL:1 MANE Select	c.-189G>C		upstream_gene	N/A	ENSP00000351137.3	Q9HCS7

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29476 AN: 152098 Hom.: 3013 Cov.: 32

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.482

Gnomad AMR AF: 0.174

Gnomad ASJ AF: 0.198

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.205

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.228

Gnomad OTH AF: 0.192

GnomAD4 exome AF: 0.225 AC: 295270 AN: 1312380 Hom.: 34433 Cov.: 20 AF XY: 0.224 AC XY: 145292 AN XY: 649488

African (AFR) AF: 0.146 AC: 4352 AN: 29836

American (AMR) AF: 0.159 AC: 5398 AN: 33950

Ashkenazi Jewish (ASJ) AF: 0.208 AC: 5041 AN: 24256

East Asian (EAS) AF: 0.130 AC: 4577 AN: 35160

South Asian (SAS) AF: 0.160 AC: 12367 AN: 77132

European-Finnish (FIN) AF: 0.218 AC: 7980 AN: 36584

Middle Eastern (MID) AF: 0.194 AC: 1066 AN: 5506

European-Non Finnish (NFE) AF: 0.239 AC: 242516 AN: 1014662

Other (OTH) AF: 0.217 AC: 11973 AN: 55294

GnomAD4 genome AF: 0.194 AC: 29493 AN: 152216 Hom.: 3015 Cov.: 32 AF XY: 0.191 AC XY: 14239 AN XY: 74408

African (AFR) AF: 0.149 AC: 6192 AN: 41532

American (AMR) AF: 0.174 AC: 2654 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.198 AC: 687 AN: 3468

East Asian (EAS) AF: 0.121 AC: 628 AN: 5194

South Asian (SAS) AF: 0.157 AC: 757 AN: 4826

European-Finnish (FIN) AF: 0.205 AC: 2172 AN: 10588

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.228 AC: 15514 AN: 68010

Other (OTH) AF: 0.192 AC: 405 AN: 2112

Alfa AF: 0.118 Hom.: 188

Bravo AF: 0.193

Asia WGS AF: 0.148 AC: 516 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.47
DANN	Benign	0.61
PhyloP100		-1.5
PromoterAI		-0.12	Neutral
Mutation Taster		=100/0	polymorphism

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; COSMIC: COSV60696697;