rs201060739

Variant names:

• chrX-154531928-GTCC-G
• rs201060739
• NM_001360016.2:c.*69_*71delGGA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001360016.2(G6PD):​c.*69_*71delGGA 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
• Publications: 2 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, Labcorp Genetics (formerly Invitae), Ambry Genetics
• 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 -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 VariationId 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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	G6PD	NM_001360016.2	MANE Select	c.*69_*71delGGA		3_prime_UTR	Exon 13 of 13	NP_001346945.1	A0A384NL00
	G6PD	NM_000402.4		c.*69_*71delGGA		3_prime_UTR	Exon 13 of 13	NP_000393.4	P11413-3
	G6PD	NM_001042351.3		c.*69_*71delGGA		3_prime_UTR	Exon 13 of 13	NP_001035810.1	P11413-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	G6PD	ENST00000393562.10	TSL:1 MANE Select	c.*69_*71delGGA		3_prime_UTR	Exon 13 of 13	ENSP00000377192.3	P11413-1
	G6PD	ENST00000915896.1		c.*69_*71delGGA		3_prime_UTR	Exon 13 of 13	ENSP00000585955.1
	G6PD	ENST00000439227.6	TSL:5	c.*69_*71delGGA		3_prime_UTR	Exon 13 of 13	ENSP00000395599.2	E7EUI8

Frequencies

GnomAD3 genomes AF: 0.0296 AC: 3202 AN: 108141 Hom.: 128 Cov.: 19

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

African (AFR) AF: 0.110 AC: 2824 AN: 25643

American (AMR) AF: 0.00749 AC: 221 AN: 29508

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18304

East Asian (EAS) AF: 0.00 AC: 0 AN: 28366

South Asian (SAS) AF: 0.000302 AC: 15 AN: 49683

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37126

Middle Eastern (MID) AF: 0.00458 AC: 18 AN: 3933

European-Non Finnish (NFE) AF: 0.000127 AC: 104 AN: 821167

Other (OTH) AF: 0.00905 AC: 403 AN: 44547

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

African (AFR) AF: 0.102 AC: 3013 AN: 29508

American (AMR) AF: 0.0143 AC: 146 AN: 10240

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2593

East Asian (EAS) AF: 0.00 AC: 0 AN: 3415

South Asian (SAS) AF: 0.00 AC: 0 AN: 2456

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5685

Middle Eastern (MID) AF: 0.00472 AC: 1 AN: 212

European-Non Finnish (NFE) AF: 0.000366 AC: 19 AN: 51947

Other (OTH) AF: 0.0232 AC: 34 AN: 1465

Alfa AF: 0.0285 Hom.: 82

Bravo AF: 0.0384

Asia WGS AF: 0.00837 AC: 22 AN: 2520

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.068
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs201060739; hg19: chrX-153760143;