chrX-154545836-C-CA

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

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

Scores

Not classified

Clinical Significance

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

Conservation

PhyloP100: 0.539
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]
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]

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ACMG classification

Classification made for transcript

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
G6PDNM_001360016.2 linkuse as main transcriptc.120+199_120+200insT intron_variant ENST00000393562.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
G6PDENST00000393562.10 linkuse as main transcriptc.120+199_120+200insT intron_variant 1 NM_001360016.2 P4P11413-1

Frequencies

GnomAD3 genomes
AF:
0.0498
AC:
1839
AN:
36934
Hom.:
79
Cov.:
20
AF XY:
0.0155
AC XY:
120
AN XY:
7756
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.:
0
Cov.:
0
AF XY:
0.0000167
AC XY:
1
AN XY:
59726
show subpopulations
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
show subpopulations
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
LINK: link

Submissions by phenotype

Anemia, nonspherocytic hemolytic, due to G6PD deficiency Benign:1
Benign, criteria provided, single submittercurationDunham Lab, University of WashingtonAug 12, 2022Variant found at a frequency of 5.5% in gnomAD (BA1) and previously interpreted as benign (BP6). -
not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxOct 06, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs781893284; hg19: chrX-153774051; API