X-154545836-CAAAAAAAAAAA-CAAAAAAAA

Variant names:

Variant summary

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

The NM_001360016.2(G6PD):c.120+197_120+199delTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0188 in 268,163 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000081 ( 0 hom., 0 hem., cov: 20)

Exomes 𝑓: 0.022 ( 0 hom. 0 hem. )

Consequence

G6PD
NM_001360016.2 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.539

Publications

0 publications found

Variant links:

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]

G6PD links:

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

IKBKG links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
G6PD	NM_001360016.2	MANE Select	c.120+197_120+199delTTT	intron	N/A	NP_001346945.1	A0A384NL00
G6PD	NM_000402.4		c.210+197_210+199delTTT	intron	N/A	NP_000393.4	P11413-3
G6PD	NM_001042351.3		c.120+197_120+199delTTT	intron	N/A	NP_001035810.1	P11413-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
G6PD	ENST00000393562.10	TSL:1 MANE Select	c.120+197_120+199delTTT	intron	N/A	ENSP00000377192.3	P11413-1
IKBKG	ENST00000618670.4	TSL:1	c.189+3402_189+3404delAAA	intron	N/A	ENSP00000483825.1	Q9Y6K9-2
IKBKG	ENST00000612051.1	TSL:1	n.124+3467_124+3469delAAA	intron	N/A	ENSP00000480431.1	A0A087WWQ9

Frequencies

GnomAD3 genomes

AF:

0.0000808

AC:

AN:

37115

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000970

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:

0.00141

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0218

AC:

5036

AN:

231048

Hom.:

AF XY:

0.00

AC XY:

AN XY:

68268

show subpopulations

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

African (AFR)

AF:

0.0221

AC:

150

AN:

6798

American (AMR)

AF:

0.0246

AC:

260

AN:

10553

Ashkenazi Jewish (ASJ)

AF:

0.0249

AC:

157

AN:

6307

East Asian (EAS)

AF:

0.0240

AC:

343

AN:

14297

South Asian (SAS)

AF:

0.0122

AC:

258

AN:

21101

European-Finnish (FIN)

AF:

0.0236

AC:

326

AN:

13839

Middle Eastern (MID)

AF:

0.0272

AC:

AN:

845

European-Non Finnish (NFE)

AF:

0.0222

AC:

3212

AN:

144380

Other (OTH)

AF:

0.0237

AC:

307

AN:

12928

⚠️ 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.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.271

Heterozygous variant carriers

486

972

1457

1943

2429

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

112

140

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000808

AC:

AN:

37115

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

7793

show subpopulations

African (AFR)

AF:

0.0000970

AC:

AN:

10309

American (AMR)

AF:

0.00

AC:

AN:

3030

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

934

East Asian (EAS)

AF:

0.00

AC:

AN:

1319

South Asian (SAS)

AF:

0.00

AC:

AN:

904

European-Finnish (FIN)

AF:

0.00141

AC:

AN:

1418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

18474

Other (OTH)

AF:

0.00

AC:

AN:

460

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.54

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over