X-154534556-G-C

Variant names:

• chrX-154534556-G-C
• rs2515904
• NM_001360016.2:c.486-60C>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001360016.2(G6PD):​c.486-60C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00843 in 1,185,278 control chromosomes in the GnomAD database, including 544 homozygotes. There are 2,656 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.043 (258 hom., 1307 hem., cov: 23)
  • Exomes 𝑓: 0.0048 (286 hom. 1349 hem.)
• Consequence: G6PD NM_001360016.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts P:1 B:4
• Conservation: PhyloP100: -0.00100
• Publications: 19 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant X-154534556-G-C is Benign according to our data. Variant chrX-154534556-G-C is described in ClinVar as Benign. ClinVar VariationId is 10374.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.147 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	G6PD	NM_001360016.2	MANE Select	c.486-60C>G		intron	N/A	NP_001346945.1
	G6PD	NM_000402.4		c.576-60C>G		intron	N/A	NP_000393.4
	G6PD	NM_001042351.3		c.486-60C>G		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.486-60C>G		intron	N/A	ENSP00000377192.3
	G6PD	ENST00000696421.1		c.486-60C>G		intron	N/A	ENSP00000512616.1
	G6PD	ENST00000369620.6	TSL:5	c.486-60C>G		intron	N/A	ENSP00000358633.2

Frequencies

GnomAD3 genomes AF: 0.0433 AC: 4845 AN: 111849 Hom.: 258 Cov.: 23

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0157

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000367

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00418

Gnomad NFE AF: 0.000283

Gnomad OTH AF: 0.0351

GnomAD4 exome AF: 0.00478 AC: 5133 AN: 1073378 Hom.: 286 AF XY: 0.00393 AC XY: 1349 AN XY: 343300

African (AFR) AF: 0.166 AC: 4336 AN: 26077

American (AMR) AF: 0.00644 AC: 225 AN: 34946

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19204

East Asian (EAS) AF: 0.00 AC: 0 AN: 30069

South Asian (SAS) AF: 0.000356 AC: 19 AN: 53388

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34275

Middle Eastern (MID) AF: 0.00537 AC: 21 AN: 3909

European-Non Finnish (NFE) AF: 0.000117 AC: 97 AN: 826150

Other (OTH) AF: 0.00959 AC: 435 AN: 45360

GnomAD4 genome AF: 0.0434 AC: 4854 AN: 111900 Hom.: 258 Cov.: 23 AF XY: 0.0383 AC XY: 1307 AN XY: 34094

African (AFR) AF: 0.150 AC: 4616 AN: 30740

American (AMR) AF: 0.0157 AC: 168 AN: 10691

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2651

East Asian (EAS) AF: 0.00 AC: 0 AN: 3517

South Asian (SAS) AF: 0.000368 AC: 1 AN: 2714

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6207

Middle Eastern (MID) AF: 0.00461 AC: 1 AN: 217

European-Non Finnish (NFE) AF: 0.000283 AC: 15 AN: 52956

Other (OTH) AF: 0.0347 AC: 53 AN: 1529

Alfa AF: 0.0352 Hom.: 113

Bravo AF: 0.0492

ClinVar

Significance: Benign

Submissions summary: Pathogenic:1 Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

G6PD deficiency Pathogenic:1 Benign:1

Jan 06, 2020

Reproductive Health Research and Development, BGI Genomics

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: curation

NG_009015.2(NM_001042351.2):c.486-60C>G in the gene G6PD has an allele frequency of 0.155 in African subpopulation in the gnomAD database. A total of 43 homozygous and 316 hemizygotes occurrences are observed in the gnomAD database. This evidence suggests the variant to be classified as benign. ACMG/AMP criteria applied: BA1, BS2.

Sep 28, 1979

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Jul 05, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Apr 19, 2023

Department of Pathology and Laboratory Medicine, Sinai Health System

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: research

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.58
DANN	Benign	0.39
PhyloP100		-0.0010
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	disease causing (ClinVar)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2515904; hg19: chrX-153762771;