rs9904733

chr17-3626942-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013276.4(SHPK):c.311-2711G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.061 in 152,112 control chromosomes in the GnomAD database, including 327 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.061 (327 hom., cov: 31)
• Consequence: SHPK NM_013276.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0200

Genes affected

SHPK (HGNC:1492): (sedoheptulokinase) The protein encoded by this gene has weak homology to several carbohydrate kinases, a class of proteins involved in the phosphorylation of sugars as they enter a cell, inhibiting return across the cell membrane. Sequence variation between this novel gene and known carbohydrate kinases suggests the possibility of a different substrate, cofactor or changes in kinetic properties distinguishing it from other carbohydrate kinases. The gene resides in a region commonly deleted in cystinosis patients, suggesting a role as a modifier for the cystinosis phenotype. The genomic region is also rich in Alu repetitive sequences, frequently involved in chromosomal rearrangements. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0713 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SHPK	NM_013276.4	c.311-2711G>A		intron_variant		ENST00000225519.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SHPK	ENST00000225519.5	c.311-2711G>A		intron_variant		1	NM_013276.4	P1

Frequencies

GnomAD3 genomes AF: 0.0611 AC: 9281 AN: 151994 Hom.: 327 Cov.: 31

Gnomad AFR AF: 0.0644

Gnomad AMI AF: 0.0899

Gnomad AMR AF: 0.0313

Gnomad ASJ AF: 0.0577

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0582

Gnomad FIN AF: 0.0491

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0729

Gnomad OTH AF: 0.0375

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0610 AC: 9286 AN: 152112 Hom.: 327 Cov.: 31 AF XY: 0.0600 AC XY: 4460 AN XY: 74358

Gnomad4 AFR AF: 0.0643

Gnomad4 AMR AF: 0.0312

Gnomad4 ASJ AF: 0.0577

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.0584

Gnomad4 FIN AF: 0.0491

Gnomad4 NFE AF: 0.0729

Gnomad4 OTH AF: 0.0371

Alfa AF: 0.0660 Hom.: 365

Bravo AF: 0.0586

Asia WGS AF: 0.0270 AC: 93 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
Cadd	Benign	4.3
Dann	Benign	0.80

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: rs9904733; hg19: chr17-3530236;