19-7629716-C-G

Variant names:

• chr19-7629716-C-G
• rs794085
• NM_020196.3:c.-189G>C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_020196.3(XAB2):​c.-189G>C variant causes a upstream gene 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: XAB2 NM_020196.3 upstream_gene
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.54

Genes affected

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]

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XAB2	NM_020196.3	c.-189G>C		upstream_gene_variant		ENST00000358368.5	NP_064581.2
PET100	NM_001171155.2	c.-118C>G		upstream_gene_variant		ENST00000594797.6	NP_001164626.1
STXBP2	NM_001414484.1	c.-315C>G		upstream_gene_variant			NP_001401413.1
PET100	NR_033242.2	n.-77C>G		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XAB2	ENST00000358368.5	c.-189G>C		upstream_gene_variant		1	NM_020196.3	ENSP00000351137.3
PET100	ENST00000594797.6	c.-118C>G		upstream_gene_variant		1	NM_001171155.2	ENSP00000470539.1
ENSG00000268400	ENST00000698368.1	n.-118C>G		upstream_gene_variant				ENSP00000513686.1

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

Gnomad4 AFR exome AF: 0.146

Gnomad4 AMR exome AF: 0.159

Gnomad4 ASJ exome AF: 0.208

Gnomad4 EAS exome AF: 0.130

Gnomad4 SAS exome AF: 0.160

Gnomad4 FIN exome AF: 0.218

Gnomad4 NFE exome AF: 0.239

Gnomad4 OTH exome AF: 0.217

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

Gnomad4 AFR AF: 0.149

Gnomad4 AMR AF: 0.174

Gnomad4 ASJ AF: 0.198

Gnomad4 EAS AF: 0.121

Gnomad4 SAS AF: 0.157

Gnomad4 FIN AF: 0.205

Gnomad4 NFE AF: 0.228

Gnomad4 OTH AF: 0.192

Alfa AF: 0.118 Hom.: 188

Bravo AF: 0.193

Asia WGS AF: 0.148 AC: 516 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 23, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.47
DANN	Benign	0.61

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs794085; hg19: chr19-7694602; COSMIC: COSV60696697;