X-154545836-C-CA

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001360016.2(G6PD):c.120+199_120+200insT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.050 (80 hom., 118 hem., cov: 20)
  • Exomes 𝑓: 0.058 (0 hom. 1 hem.)
• Consequence: G6PD NM_001360016.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• 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 -16 ACMG points.

• BP6: Variant X-154545836-C-CA is Benign according to our data. Variant chrX-154545836-C-CA is described in ClinVar as [Benign]. Clinvar id is 1246459.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.143 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
G6PD	NM_001360016.2	c.120+199_120+200insT		intron_variant		ENST00000393562.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
G6PD	ENST00000393562.10	c.120+199_120+200insT		intron_variant		1	NM_001360016.2	P4

Frequencies

GnomAD3 genomes AF: 0.0498 AC: 1839 AN: 36934 Hom.: 79 Cov.: 20 AF XY: 0.0155 AC XY: 120 AN XY: 7756

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.00515

Gnomad AMR AF: 0.0271

Gnomad ASJ AF: 0.0129

Gnomad EAS AF: 0.0130

Gnomad SAS AF: 0.00333

Gnomad FIN AF: 0.00423

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00893

Gnomad OTH AF: 0.0435

GnomAD4 exome AF: 0.0579 AC: 13213 AN: 228332 Hom.: 0 Cov.: 0 AF XY: 0.0000167 AC XY: 1 AN XY: 59726

Gnomad4 AFR exome AF: 0.0907

Gnomad4 AMR exome AF: 0.0509

Gnomad4 ASJ exome AF: 0.0656

Gnomad4 EAS exome AF: 0.0642

Gnomad4 SAS exome AF: 0.0303

Gnomad4 FIN exome AF: 0.0579

Gnomad4 NFE exome AF: 0.0594

Gnomad4 OTH exome AF: 0.0626

GnomAD4 genome AF: 0.0497 AC: 1836 AN: 36942 Hom.: 80 Cov.: 20 AF XY: 0.0152 AC XY: 118 AN XY: 7752

Gnomad4 AFR AF: 0.149

Gnomad4 AMR AF: 0.0271

Gnomad4 ASJ AF: 0.0129

Gnomad4 EAS AF: 0.0130

Gnomad4 SAS AF: 0.00336

Gnomad4 FIN AF: 0.00423

Gnomad4 NFE AF: 0.00894

Gnomad4 OTH AF: 0.0425

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Anemia, nonspherocytic hemolytic, due to G6PD deficiency Benign:1

Benign, criteria provided, single submitter

curation

Dunham Lab, University of Washington

Aug 12, 2022

Variant found at a frequency of 5.5% in gnomAD (BA1) and previously interpreted as benign (BP6). -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 06, 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;