rs9904733

Variant names:

• chr17-3626942-C-T
• rs9904733
• NM_013276.4:c.311-2711G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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]

SHPK Gene-Disease associations (from GenCC):

• isolated sedoheptulokinase deficiency

  Inheritance: AR, Unknown Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics

ENSG00000262304 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SHPK	NM_013276.4	c.311-2711G>A		intron_variant	Intron 2 of 6	ENST00000225519.5	NP_037408.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SHPK	ENST00000225519.5	c.311-2711G>A		intron_variant	Intron 2 of 6	1	NM_013276.4	ENSP00000225519.3
ENSG00000262304	ENST00000572919.1	n.311-2711G>A		intron_variant	Intron 2 of 13	5		ENSP00000461416.1

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

African (AFR) AF: 0.0643 AC: 2671 AN: 41526

American (AMR) AF: 0.0312 AC: 476 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.0577 AC: 200 AN: 3468

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5176

South Asian (SAS) AF: 0.0584 AC: 281 AN: 4808

European-Finnish (FIN) AF: 0.0491 AC: 520 AN: 10588

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0729 AC: 4959 AN: 67980

Other (OTH) AF: 0.0371 AC: 78 AN: 2100

Alfa AF: 0.0644 Hom.: 540

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
PhyloP100		0.020
Mutation Taster		=100/0	polymorphism (auto)

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: rs9904733; hg19: chr17-3530236;