17-3616660-G-T

Variant names:

• chr17-3616660-G-T
• rs224498
• NM_013276.4:c.824-1123C>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.824-1123C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.679 in 152,154 control chromosomes in the GnomAD database, including 35,921 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 0.68 (35921 hom., cov: 33)
• Consequence: SHPK NM_013276.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0360
• Publications: 8 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: MODERATE, SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia, Orphanet

ENSG00000262304 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.973 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013276.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHPK	NM_013276.4	MANE Select	c.824-1123C>A		intron	N/A	NP_037408.2	Q9UHJ6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHPK	ENST00000225519.5	TSL:1 MANE Select	c.824-1123C>A		intron	N/A	ENSP00000225519.3	Q9UHJ6
	ENSG00000262304	ENST00000572919.1	TSL:5	n.824-1123C>A		intron	N/A	ENSP00000461416.1

Frequencies

GnomAD3 genomes AF: 0.679 AC: 103165 AN: 152036 Hom.: 35887 Cov.: 33

Gnomad AFR AF: 0.798

Gnomad AMI AF: 0.587

Gnomad AMR AF: 0.702

Gnomad ASJ AF: 0.620

Gnomad EAS AF: 0.995

Gnomad SAS AF: 0.757

Gnomad FIN AF: 0.603

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.587

Gnomad OTH AF: 0.677

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

GnomAD4 genome AF: 0.679 AC: 103251 AN: 152154 Hom.: 35921 Cov.: 33 AF XY: 0.681 AC XY: 50646 AN XY: 74368

African (AFR) AF: 0.797 AC: 33123 AN: 41538

American (AMR) AF: 0.703 AC: 10733 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.620 AC: 2150 AN: 3470

East Asian (EAS) AF: 0.995 AC: 5168 AN: 5192

South Asian (SAS) AF: 0.756 AC: 3648 AN: 4826

European-Finnish (FIN) AF: 0.603 AC: 6371 AN: 10568

Middle Eastern (MID) AF: 0.634 AC: 185 AN: 292

European-Non Finnish (NFE) AF: 0.587 AC: 39899 AN: 67964

Other (OTH) AF: 0.681 AC: 1439 AN: 2114

Alfa AF: 0.624 Hom.: 95270

Bravo AF: 0.693

Asia WGS AF: 0.879 AC: 3056 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.3
DANN	Benign	0.27
PhyloP100		-0.036
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: rs224498; hg19: chr17-3519954;