1-9246952-TC-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_004285.4(H6PD):c.628-6del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000694 in 1,554,890 control chromosomes in the GnomAD database, including 4 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0028 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00046 (3 hom.)
• Consequence: H6PD NM_004285.4 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.00

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 Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 1-9246952-TC-T is Benign according to our data. Variant chr1-9246952-TC-T is described in ClinVar as [Benign]. Clinvar id is 1987851.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
H6PD	NM_004285.4	c.628-6del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000377403.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
H6PD	ENST00000377403.7	c.628-6del		splice_polypyrimidine_tract_variant, intron_variant		1	NM_004285.4	P1
H6PD	ENST00000602477.1	c.661-6del		splice_polypyrimidine_tract_variant, intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.00280 AC: 422 AN: 150826 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00985

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000463

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000958

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00145

GnomAD3 exomes AF: 0.000786 AC: 196 AN: 249472 Hom.: 2 AF XY: 0.000614 AC XY: 83 AN XY: 135148

Gnomad AFR exome AF: 0.0105

Gnomad AMR exome AF: 0.000231

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000272

Gnomad SAS exome AF: 0.0000654

Gnomad FIN exome AF: 0.0000953

Gnomad NFE exome AF: 0.0000621

Gnomad OTH exome AF: 0.000492

GnomAD4 exome AF: 0.000464 AC: 652 AN: 1403950 Hom.: 3 Cov.: 26 AF XY: 0.000415 AC XY: 291 AN XY: 701202

Gnomad4 AFR exome AF: 0.0102

Gnomad4 AMR exome AF: 0.000270

Gnomad4 ASJ exome AF: 0.000117

Gnomad4 EAS exome AF: 0.000103

Gnomad4 SAS exome AF: 0.000176

Gnomad4 FIN exome AF: 0.000133

Gnomad4 NFE exome AF: 0.000214

Gnomad4 OTH exome AF: 0.000893

GnomAD4 genome AF: 0.00283 AC: 427 AN: 150940 Hom.: 1 Cov.: 32 AF XY: 0.00295 AC XY: 217 AN XY: 73616

Gnomad4 AFR AF: 0.00994

Gnomad4 AMR AF: 0.000462

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000958

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.00143

Alfa AF: 0.000305 Hom.: 0

Bravo AF: 0.00306

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 14, 2022

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Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs201586222; hg19: chr1-9307011;