X-154545836-CAAAAAAAAAAA-CAAAAAAAAAAAA

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_001360016.2(G6PD):c.120+199dupT 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

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

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: Benign. The variant received -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 VariationId 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.

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+199dupT	intron	N/A	NP_001346945.1	A0A384NL00
G6PD	NM_000402.4		c.210+199dupT	intron	N/A	NP_000393.4	P11413-3
G6PD	NM_001042351.3		c.120+199dupT	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+199dupT	intron	N/A	ENSP00000377192.3	P11413-1
IKBKG	ENST00000618670.4	TSL:1	c.189+3404dupA	intron	N/A	ENSP00000483825.1	Q9Y6K9-2
IKBKG	ENST00000612051.1	TSL:1	n.124+3469dupA	intron	N/A	ENSP00000480431.1	A0A087WWQ9

Frequencies

GnomAD3 genomes

AF:

0.0498

AC:

1839

AN:

36934

Hom.:

Cov.:

show subpopulations

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.:

Cov.:

AF XY:

0.0000167

AC XY:

AN XY:

59726

show subpopulations

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

African (AFR)

AF:

0.0907

AC:

606

AN:

6679

American (AMR)

AF:

0.0509

AC:

542

AN:

10647

Ashkenazi Jewish (ASJ)

AF:

0.0656

AC:

410

AN:

6249

East Asian (EAS)

AF:

0.0642

AC:

905

AN:

14099

South Asian (SAS)

AF:

0.0303

AC:

618

AN:

20427

European-Finnish (FIN)

AF:

0.0579

AC:

800

AN:

13814

Middle Eastern (MID)

AF:

0.0641

AC:

AN:

842

European-Non Finnish (NFE)

AF:

0.0594

AC:

8468

AN:

142632

Other (OTH)

AF:

0.0626

AC:

810

AN:

12943

⚠️ 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: 0.336

Heterozygous variant carriers

851

1702

2553

3404

4255

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

176

264

352

440

<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:

0.0497

AC:

1836

AN:

36942

Hom.:

Cov.:

AF XY:

0.0152

AC XY:

118

AN XY:

7752

show subpopulations

African (AFR)

AF:

0.149

AC:

1531

AN:

10291

American (AMR)

AF:

0.0271

AC:

AN:

3026

Ashkenazi Jewish (ASJ)

AF:

0.0129

AC:

AN:

930

East Asian (EAS)

AF:

0.0130

AC:

AN:

1304

South Asian (SAS)

AF:

0.00336

AC:

AN:

892

European-Finnish (FIN)

AF:

0.00423

AC:

AN:

1418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00894

AC:

164

AN:

18354

Other (OTH)

AF:

0.0425

AC:

AN:

471

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

140

211

281

351

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

<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:

0.000957

Hom.:

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Anemia, nonspherocytic hemolytic, due to G6PD deficiency (1)

not provided (1)

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