NM_001360016.2:c.1431C>T

Variant names:

• chrX-154532214-G-A
• rs77214077
• NM_001360016.2:c.1431C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001360016.2(G6PD):​c.1431C>T​(p.Pro477Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0043 in 1,209,236 control chromosomes in the GnomAD database, including 161 homozygotes. There are 1,369 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.022 (75 hom., 648 hem., cov: 23)
  • Exomes 𝑓: 0.0025 (86 hom. 721 hem.)
• Consequence: G6PD NM_001360016.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -1.06
• Publications: 10 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant X-154532214-G-A is Benign according to our data. Variant chrX-154532214-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 93496.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.06 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0761 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.1431C>T	p.Pro477Pro	synonymous	Exon 12 of 13	NP_001346945.1	A0A384NL00
	G6PD	NM_000402.4		c.1521C>T	p.Pro507Pro	synonymous	Exon 12 of 13	NP_000393.4	P11413-3
	G6PD	NM_001042351.3		c.1431C>T	p.Pro477Pro	synonymous	Exon 12 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.1431C>T	p.Pro477Pro	synonymous	Exon 12 of 13	ENSP00000377192.3	P11413-1
	G6PD	ENST00000696421.1		c.1431C>T	p.Pro477Pro	synonymous	Exon 12 of 13	ENSP00000512616.1	A0A8Q3SIS5
	G6PD	ENST00000369620.6	TSL:5	c.1569C>T	p.Pro523Pro	synonymous	Exon 12 of 13	ENSP00000358633.2	P11413-2

Frequencies

GnomAD3 genomes AF: 0.0223 AC: 2485 AN: 111280 Hom.: 74 Cov.: 23

Gnomad AFR AF: 0.0783

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00521

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000373

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000189

Gnomad OTH AF: 0.0167

GnomAD2 exomes AF: 0.00676 AC: 1231 AN: 182188 AF XY: 0.00402

Gnomad AFR exome AF: 0.0875

Gnomad AMR exome AF: 0.00241

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000123

Gnomad OTH exome AF: 0.00245

GnomAD4 exome AF: 0.00246 AC: 2702 AN: 1097908 Hom.: 86 Cov.: 37 AF XY: 0.00198 AC XY: 721 AN XY: 363322

African (AFR) AF: 0.0868 AC: 2291 AN: 26403

American (AMR) AF: 0.00279 AC: 98 AN: 35187

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19381

East Asian (EAS) AF: 0.00 AC: 0 AN: 30203

South Asian (SAS) AF: 0.000166 AC: 9 AN: 54110

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40389

Middle Eastern (MID) AF: 0.00436 AC: 18 AN: 4132

European-Non Finnish (NFE) AF: 0.0000629 AC: 53 AN: 842021

Other (OTH) AF: 0.00506 AC: 233 AN: 46082

GnomAD4 genome AF: 0.0224 AC: 2499 AN: 111328 Hom.: 75 Cov.: 23 AF XY: 0.0193 AC XY: 648 AN XY: 33602

African (AFR) AF: 0.0787 AC: 2409 AN: 30620

American (AMR) AF: 0.00521 AC: 55 AN: 10561

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2642

East Asian (EAS) AF: 0.00 AC: 0 AN: 3542

South Asian (SAS) AF: 0.00 AC: 0 AN: 2673

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6006

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 216

European-Non Finnish (NFE) AF: 0.000189 AC: 10 AN: 52877

Other (OTH) AF: 0.0165 AC: 25 AN: 1518

Alfa AF: 0.0118 Hom.: 343

Bravo AF: 0.0263

EpiCase AF: 0.000109

EpiControl AF: 0.000416

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	Anemia, nonspherocytic hemolytic, due to G6PD deficiency (2)
-	-	1	G6PD deficiency (1)
-	-	1	G6PD-related disorder (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.7
DANN	Benign	0.38
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs77214077; hg19: chrX-153760429;