rs111485003

Variant names:

• chrX-154531696-A-G
• rs111485003
• NM_001360016.2:c.*304T>C

Your query was ambiguous. Multiple possible variants found:

• chrX-154531696-A-G
• chrX-154531696-A-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001360016.2(G6PD):​c.*304T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: G6PD NM_001360016.2 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.132

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]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant X-154531696-A-G is Benign according to our data. Variant chrX-154531696-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1722655.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
G6PD	NM_001360016.2	c.*304T>C		3_prime_UTR_variant	Exon 13 of 13	ENST00000393562.10	NP_001346945.1
G6PD	NM_000402.4	c.*304T>C		3_prime_UTR_variant	Exon 13 of 13		NP_000393.4
G6PD	NM_001042351.3	c.*304T>C		3_prime_UTR_variant	Exon 13 of 13		NP_001035810.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
G6PD	ENST00000393562	c.*304T>C		3_prime_UTR_variant	Exon 13 of 13	1	NM_001360016.2	ENSP00000377192.3

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 254187 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 71941

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 23

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

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

Dec 05, 2024

Dunham Lab, University of Washington

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: curation

Variant found in individuals without G6PD deficiency whose activity in RBCs is within normal range (BS2); only occurance in an individual with deficiency has other SNVs that were found alone to contribute to deficiency (BP5). Not predicted to alter mRNA folding or miRNA target sites (BP4). Post_P 0.0014 (odds of pathogenicity 0.0124, Prior_P 0.1). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.9
DANN	Benign	0.48

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

Publications

LitVar

Other links and lift over

dbSNP: rs111485003; hg19: chrX-153759911;