chr19-7629875-G-C

Variant names:

• chr19-7629875-G-C
• rs989708248
• NM_001171155.2:c.27+15G>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001171155.2(PET100):​c.27+15G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000727 in 1,376,418 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: PET100 NM_001171155.2 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.13
• 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]

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 -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 19-7629875-G-C is Benign according to our data. Variant chr19-7629875-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2711496.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001171155.2. 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
	PET100	NM_001171155.2	MANE Select	c.27+15G>C		intron	N/A	NP_001164626.1	P0DJ07
	STXBP2	NM_001414484.1		c.-171+15G>C		intron	N/A	NP_001401413.1
	PET100	NR_033242.2		n.68+15G>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PET100	ENST00000594797.6	TSL:1 MANE Select	c.27+15G>C		intron	N/A	ENSP00000470539.1	P0DJ07
	ENSG00000268400	ENST00000698368.1		n.27+15G>C		intron	N/A	ENSP00000513686.1	A0A8V8TM65
	PET100	ENST00000923271.1		c.27+15G>C		intron	N/A	ENSP00000593330.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.27e-7 AC: 1 AN: 1376418 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 678512

African (AFR) AF: 0.0000320 AC: 1 AN: 31274

American (AMR) AF: 0.00 AC: 0 AN: 34150

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24704

East Asian (EAS) AF: 0.00 AC: 0 AN: 35610

South Asian (SAS) AF: 0.00 AC: 0 AN: 78188

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34784

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5656

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1074462

Other (OTH) AF: 0.00 AC: 0 AN: 57590

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	12
DANN	Benign	0.72
PhyloP100		1.1
PromoterAI		0.0011	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs989708248; hg19: chr19-7694761;