17-3615766-T-G

Variant names:

• chr17-3615766-T-G
• rs150854
• NM_013276.4:c.824-229A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013276.4(SHPK):​c.824-229A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.349 in 138,108 control chromosomes in the GnomAD database, including 10,753 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 0.35 (10753 hom., cov: 28)
• Consequence: SHPK NM_013276.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0310
• Publications: 5 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.652 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHPK	NM_013276.4	c.824-229A>C		intron_variant	Intron 5 of 6	ENST00000225519.5	NP_037408.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SHPK	ENST00000225519.5	c.824-229A>C		intron_variant	Intron 5 of 6	1	NM_013276.4	ENSP00000225519.3
ENSG00000262304	ENST00000572919.1	n.824-229A>C		intron_variant	Intron 5 of 13	5		ENSP00000461416.1

Frequencies

GnomAD3 genomes AF: 0.350 AC: 48249 AN: 138012 Hom.: 10755 Cov.: 28

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.341

Gnomad AMR AF: 0.458

Gnomad ASJ AF: 0.415

Gnomad EAS AF: 0.672

Gnomad SAS AF: 0.427

Gnomad FIN AF: 0.463

Gnomad MID AF: 0.359

Gnomad NFE AF: 0.420

Gnomad OTH AF: 0.395

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

GnomAD4 genome AF: 0.349 AC: 48226 AN: 138108 Hom.: 10753 Cov.: 28 AF XY: 0.354 AC XY: 23862 AN XY: 67360

African (AFR) AF: 0.122 AC: 4791 AN: 39212

American (AMR) AF: 0.458 AC: 6135 AN: 13386

Ashkenazi Jewish (ASJ) AF: 0.415 AC: 1317 AN: 3176

East Asian (EAS) AF: 0.671 AC: 3063 AN: 4562

South Asian (SAS) AF: 0.426 AC: 1874 AN: 4400

European-Finnish (FIN) AF: 0.463 AC: 4191 AN: 9050

Middle Eastern (MID) AF: 0.356 AC: 89 AN: 250

European-Non Finnish (NFE) AF: 0.420 AC: 25744 AN: 61356

Other (OTH) AF: 0.392 AC: 736 AN: 1878

Alfa AF: 0.418 Hom.: 37650

Bravo AF: 0.363

Asia WGS AF: 0.435 AC: 1369 AN: 3158

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.6
DANN	Benign	0.28
PhyloP100		-0.031
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: rs150854; hg19: chr17-3519060;