X-154545836-CAAAAAAAAAAA-CAAAAAAAAAAAAAAAA

Variant names:

• chrX-154545836-C-CAAAAA
• rs781893284
• NM_001360016.2:c.120+195_120+199dupTTTTT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001360016.2(G6PD):​c.120+195_120+199dupTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., 0 hem., cov: 20)
  • Exomes 𝑓: 0.000032 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: G6PD NM_001360016.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.539
• Publications: 0 publications found

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]

IKBKG Gene-Disease associations (from GenCC):

• ectodermal dysplasia and immunodeficiency 1

  Inheritance: XL Classification: DEFINITIVE Submitted by: G2P
• IKBKG-related immunodeficiency with or without ectodermal dysplasia

  Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
• incontinentia pigmenti

  Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, G2P, ClinGen, Orphanet
• ectodermal dysplasia and immune deficiency

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• anhidrotic ectodermal dysplasia-immunodeficiency-osteopetrosis-lymphedema syndrome

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet
• immunodeficiency 33

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001360016.2. 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
	G6PD	NM_001360016.2	MANE Select	c.120+195_120+199dupTTTTT		intron	N/A	NP_001346945.1	A0A384NL00
	G6PD	NM_000402.4		c.210+195_210+199dupTTTTT		intron	N/A	NP_000393.4	P11413-3
	G6PD	NM_001042351.3		c.120+195_120+199dupTTTTT		intron	N/A	NP_001035810.1	P11413-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	G6PD	ENST00000393562.10	TSL:1 MANE Select	c.120+195_120+199dupTTTTT		intron	N/A	ENSP00000377192.3	P11413-1
	IKBKG	ENST00000618670.4	TSL:1	c.189+3400_189+3404dupAAAAA		intron	N/A	ENSP00000483825.1	Q9Y6K9-2
	IKBKG	ENST00000612051.1	TSL:1	n.124+3465_124+3469dupAAAAA		intron	N/A	ENSP00000480431.1	A0A087WWQ9

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 37124 Hom.: 0 Cov.: 20

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000325 AC: 8 AN: 246358 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 75546

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 7176

American (AMR) AF: 0.00 AC: 0 AN: 11261

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6716

East Asian (EAS) AF: 0.00 AC: 0 AN: 15060

South Asian (SAS) AF: 0.0000428 AC: 1 AN: 23383

European-Finnish (FIN) AF: 0.0000684 AC: 1 AN: 14610

Middle Eastern (MID) AF: 0.00110 AC: 1 AN: 908

European-Non Finnish (NFE) AF: 0.0000195 AC: 3 AN: 153491

Other (OTH) AF: 0.000145 AC: 2 AN: 13753

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 37124 Hom.: 0 Cov.: 20 AF XY: 0.00 AC XY: 0 AN XY: 7794

African (AFR) AF: 0.00 AC: 0 AN: 10309

American (AMR) AF: 0.00 AC: 0 AN: 3034

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 934

East Asian (EAS) AF: 0.00 AC: 0 AN: 1319

South Asian (SAS) AF: 0.00 AC: 0 AN: 904

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 68

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 18477

Other (OTH) AF: 0.00 AC: 0 AN: 460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.54

Splicing

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

Other links and lift over

dbSNP: rs781893284; hg19: chrX-153774051;