X-154545836-CA-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001360016.2(G6PD):c.120+199del variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0071 (2 hom., 13 hem., cov: 20)
  • Exomes 𝑓: 0.15 (0 hom. 8 hem.)
• Consequence: G6PD NM_001360016.2 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.539

Genes affected

G6PD (HGNC:4057): (glucose-6-phosphate dehydrogenase) This gene encodes glucose-6-phosphate dehydrogenase. This protein is a cytosolic enzyme encoded by a housekeeping X-linked gene whose main function is to produce NADPH, a key electron donor in the defense against oxidizing agents and in reductive biosynthetic reactions. G6PD is remarkable for its genetic diversity. Many variants of G6PD, mostly produced from missense mutations, have been described with wide ranging levels of enzyme activity and associated clinical symptoms. G6PD deficiency may cause neonatal jaundice, acute hemolysis, or severe chronic non-spherocytic hemolytic anemia. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

IKBKG (HGNC:5961): (inhibitor of nuclear factor kappa B kinase regulatory subunit gamma) This gene encodes the regulatory subunit of the inhibitor of kappaB kinase (IKK) complex, which activates NF-kappaB resulting in activation of genes involved in inflammation, immunity, cell survival, and other pathways. Mutations in this gene result in incontinentia pigmenti, hypohidrotic ectodermal dysplasia, and several other types of immunodeficiencies. A pseudogene highly similar to this locus is located in an adjacent region of the X chromosome. [provided by RefSeq, Mar 2016]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant X-154545836-CA-C is Benign according to our data. Variant chrX-154545836-CA-C is described in ClinVar as [Likely_benign]. Clinvar id is 1203666.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.156 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
G6PD	NM_001360016.2	c.120+199del		intron_variant		ENST00000393562.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
G6PD	ENST00000393562.10	c.120+199del		intron_variant		1	NM_001360016.2	P4

Frequencies

GnomAD3 genomes AF: 0.00709 AC: 263 AN: 37120 Hom.: 2 Cov.: 20 AF XY: 0.00154 AC XY: 12 AN XY: 7792

Gnomad AFR AF: 0.0160

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00363

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00303

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0233

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00265

Gnomad OTH AF: 0.00217

GnomAD4 exome AF: 0.146 AC: 31212 AN: 214373 Hom.: 0 Cov.: 0 AF XY: 0.000174 AC XY: 8 AN XY: 46003

Gnomad4 AFR exome AF: 0.149

Gnomad4 AMR exome AF: 0.135

Gnomad4 ASJ exome AF: 0.155

Gnomad4 EAS exome AF: 0.162

Gnomad4 SAS exome AF: 0.0833

Gnomad4 FIN exome AF: 0.166

Gnomad4 NFE exome AF: 0.150

Gnomad4 OTH exome AF: 0.154

GnomAD4 genome AF: 0.00711 AC: 264 AN: 37128 Hom.: 2 Cov.: 20 AF XY: 0.00167 AC XY: 13 AN XY: 7788

Gnomad4 AFR AF: 0.0161

Gnomad4 AMR AF: 0.00362

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00305

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0233

Gnomad4 NFE AF: 0.00265

Gnomad4 OTH AF: 0.00212

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 05, 2019

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs781893284; hg19: chrX-153774051;