X-154531928-GTCC-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001360016.2(G6PD):c.*69_*71del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00583 in 1,166,458 control chromosomes in the GnomAD database, including 243 homozygotes. There are 1,633 hemizygotes in GnomAD. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.030 (132 hom., 663 hem., cov: 19)
  • Exomes 𝑓: 0.0034 (111 hom. 970 hem.)
• Consequence: G6PD NM_001360016.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0680

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant X-154531928-GTCC-G is Benign according to our data. Variant chrX-154531928-GTCC-G is described in ClinVar as [Benign]. Clinvar id is 1234895.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0991 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
G6PD	NM_001360016.2	c.*69_*71del		3_prime_UTR_variant	13/13	ENST00000393562.10
G6PD	NM_000402.4	c.*69_*71del		3_prime_UTR_variant	13/13
G6PD	NM_001042351.3	c.*69_*71del		3_prime_UTR_variant	13/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
G6PD	ENST00000393562.10	c.*69_*71del		3_prime_UTR_variant	13/13	1	NM_001360016.2	P4

Frequencies

GnomAD3 genomes AF: 0.0296 AC: 3202 AN: 108141 Hom.: 128 Cov.: 19 AF XY: 0.0215 AC XY: 659 AN XY: 30659

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0143

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00429

Gnomad NFE AF: 0.000366

Gnomad OTH AF: 0.0235

GnomAD4 exome AF: 0.00339 AC: 3585 AN: 1058277 Hom.: 111 AF XY: 0.00284 AC XY: 970 AN XY: 341883

Gnomad4 AFR exome AF: 0.110

Gnomad4 AMR exome AF: 0.00749

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000302

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000127

Gnomad4 OTH exome AF: 0.00905

GnomAD4 genome AF: 0.0297 AC: 3213 AN: 108181 Hom.: 132 Cov.: 19 AF XY: 0.0216 AC XY: 663 AN XY: 30709

Gnomad4 AFR AF: 0.102

Gnomad4 AMR AF: 0.0143

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000366

Gnomad4 OTH AF: 0.0232

Alfa AF: 0.0285 Hom.: 82

Bravo AF: 0.0384

Asia WGS AF: 0.00837 AC: 22 AN: 2520

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2018

- -

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: rs201060739; hg19: chrX-153760143;