rs199586268

Variant names:

• chrX-154532470-GGA-G
• rs199586268
• NM_001360016.2:c.1288-10_1288-9delTC

Your query was ambiguous. Multiple possible variants found:

• chrX-154532470-GGA-G
• chrX-154532470-GGA-GGAGA

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6 BS1 BS2_Supporting

The NM_001360016.2(G6PD):​c.1288-10_1288-9delTC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0016 in 1,209,692 control chromosomes in the GnomAD database, including 23 homozygotes. There are 514 hemizygotes in GnomAD. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.0085 (13 hom., 261 hem., cov: 24)
  • Exomes 𝑓: 0.00090 (10 hom. 253 hem.)
• Consequence: G6PD NM_001360016.2 intron
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2 B:4
• Conservation: PhyloP100: -0.707
• 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]

G6PD Gene-Disease associations (from GenCC):

• anemia, nonspherocytic hemolytic, due to G6PD deficiency

  Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• G6PD deficiency

  Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
• class I glucose-6-phosphate dehydrogenase deficiency

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP6: Variant X-154532470-GGA-G is Benign according to our data. Variant chrX-154532470-GGA-G is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 193829.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0085 (957/112639) while in subpopulation AFR AF = 0.0286 (888/31063). AF 95% confidence interval is 0.027. There are 13 homozygotes in GnomAd4. There are 261 alleles in the male GnomAd4 subpopulation. Median coverage is 24. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 13 XL geneVariant has number of homozygotes lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	G6PD	NM_001360016.2	MANE Select	c.1288-10_1288-9delTC		intron	N/A	NP_001346945.1
	G6PD	NM_000402.4		c.1378-10_1378-9delTC		intron	N/A	NP_000393.4
	G6PD	NM_001042351.3		c.1288-10_1288-9delTC		intron	N/A	NP_001035810.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	G6PD	ENST00000393562.10	TSL:1 MANE Select	c.1288-10_1288-9delTC		intron	N/A	ENSP00000377192.3
	G6PD	ENST00000696421.1		c.1288-10_1288-9delTC		intron	N/A	ENSP00000512616.1
	G6PD	ENST00000369620.6	TSL:5	c.1426-10_1426-9delTC		intron	N/A	ENSP00000358633.2

Frequencies

GnomAD3 genomes AF: 0.00848 AC: 955 AN: 112589 Hom.: 13 Cov.: 24

Gnomad AFR AF: 0.0286

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00457

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000362

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00420

Gnomad NFE AF: 0.0000940

Gnomad OTH AF: 0.00860

GnomAD2 exomes AF: 0.00237 AC: 432 AN: 182556 AF XY: 0.00162

Gnomad AFR exome AF: 0.0299

Gnomad AMR exome AF: 0.000985

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000986

Gnomad OTH exome AF: 0.000664

GnomAD4 exome AF: 0.000896 AC: 983 AN: 1097053 Hom.: 10 AF XY: 0.000698 AC XY: 253 AN XY: 362519

African (AFR) AF: 0.0292 AC: 769 AN: 26373

American (AMR) AF: 0.00142 AC: 50 AN: 35206

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19382

East Asian (EAS) AF: 0.00 AC: 0 AN: 30205

South Asian (SAS) AF: 0.000129 AC: 7 AN: 54121

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40309

Middle Eastern (MID) AF: 0.00145 AC: 6 AN: 4134

European-Non Finnish (NFE) AF: 0.0000725 AC: 61 AN: 841267

Other (OTH) AF: 0.00195 AC: 90 AN: 46056

GnomAD4 genome AF: 0.00850 AC: 957 AN: 112639 Hom.: 13 Cov.: 24 AF XY: 0.00750 AC XY: 261 AN XY: 34799

African (AFR) AF: 0.0286 AC: 888 AN: 31063

American (AMR) AF: 0.00456 AC: 49 AN: 10738

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2656

East Asian (EAS) AF: 0.00 AC: 0 AN: 3563

South Asian (SAS) AF: 0.000363 AC: 1 AN: 2757

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6235

Middle Eastern (MID) AF: 0.00463 AC: 1 AN: 216

European-Non Finnish (NFE) AF: 0.0000940 AC: 5 AN: 53195

Other (OTH) AF: 0.00849 AC: 13 AN: 1531

Alfa AF: 0.00421 Hom.: 20

Bravo AF: 0.00972

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2 Benign:4

Revision: criteria provided, conflicting classifications

Submissions by phenotype

not provided Uncertain:1 Benign:1

Sep 21, 2021

Mayo Clinic Laboratories, Mayo Clinic

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Nov 15, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

G6PD deficiency Uncertain:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not specified Benign:1

Apr 14, 2015

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Anemia, nonspherocytic hemolytic, due to G6PD deficiency Benign:1

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

G6PD-related disorder Benign:1

May 23, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.71
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs199586268; hg19: chrX-153760685;