rs112950723

Variant names:

• chrX-154531728-C-T
• rs112950723
• NM_001360016.2:c.*272G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001360016.2(G6PD):​c.*272G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000032 in 312,877 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000032 (0 hom. 1 hem.)
• Consequence: G6PD NM_001360016.2 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.83
• 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: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant X-154531728-C-T is Benign according to our data. Variant chrX-154531728-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1722666.Status of the report is criteria_provided_single_submitter, 1 stars.

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.*272G>A		3_prime_UTR	Exon 13 of 13	NP_001346945.1	A0A384NL00
	G6PD	NM_000402.4		c.*272G>A		3_prime_UTR	Exon 13 of 13	NP_000393.4	P11413-3
	G6PD	NM_001042351.3		c.*272G>A		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.*272G>A		3_prime_UTR	Exon 13 of 13	ENSP00000377192.3	P11413-1
	G6PD	ENST00000915896.1		c.*272G>A		3_prime_UTR	Exon 13 of 13	ENSP00000585955.1
	G6PD	ENST00000439227.6	TSL:5	c.*272G>A		3_prime_UTR	Exon 13 of 13	ENSP00000395599.2	E7EUI8

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.00000320 AC: 1 AN: 312877 Hom.: 0 Cov.: 4 AF XY: 0.00000997 AC XY: 1 AN XY: 100319

African (AFR) AF: 0.00 AC: 0 AN: 9283

American (AMR) AF: 0.00 AC: 0 AN: 13278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9357

East Asian (EAS) AF: 0.0000461 AC: 1 AN: 21683

South Asian (SAS) AF: 0.00 AC: 0 AN: 26261

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20854

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1881

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 191539

Other (OTH) AF: 0.00 AC: 0 AN: 18741

GnomAD4 genome Cov.: 23

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Anemia, nonspherocytic hemolytic, due to G6PD deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.5
DANN	Benign	0.60
PhyloP100		-1.8

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: rs112950723; hg19: chrX-153759943;