1-9245004-G-C

Position:

• chr1-9245004-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004285.4(H6PD):​c.70G>C​(p.Gly24Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: H6PD NM_004285.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.76

Genes affected

H6PD (HGNC:4795): (hexose-6-phosphate dehydrogenase/glucose 1-dehydrogenase) There are 2 forms of glucose-6-phosphate dehydrogenase. G form is X-linked and H form, encoded by this gene, is autosomally linked. This H form shows activity with other hexose-6-phosphates, especially galactose-6-phosphate, whereas the G form is specific for glucose-6-phosphate. Both forms are present in most tissues, but H form is not found in red cells. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1941708).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
H6PD	NM_004285.4	c.70G>C	p.Gly24Arg	missense_variant	2/5	ENST00000377403.7	NP_004276.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
H6PD	ENST00000377403.7	c.70G>C	p.Gly24Arg	missense_variant	2/5	1	NM_004285.4	ENSP00000366620.2
H6PD	ENST00000602477.1	c.103G>C	p.Gly35Arg	missense_variant	2/5	1		ENSP00000473348.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 20, 2024

The c.70G>C (p.G24R) alteration is located in exon 2 (coding exon 1) of the H6PD gene. This alteration results from a G to C substitution at nucleotide position 70, causing the glycine (G) at amino acid position 24 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	-0.034	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.43	T;T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.14
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.75	T;T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.19	T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.7	L;.
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-2.7	D;.
REVEL	Benign	0.12
Sift	Benign	0.30	T;.
Sift4G	Uncertain	0.049	D;D
Polyphen		0.11	B;.
Vest4		0.35
MutPred		0.45		Loss of catalytic residue at Q23 (P = 0.1562);.;
MVP		0.72
MPC		0.13
ClinPred		0.91	D
GERP RS		4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.23
gMVP		0.65

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-9305063;