rs7210277

Variant names:

• chr17-3626096-C-T
• rs7210277
• NM_013276.4:c.311-1865G>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.311-1865G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.1 in 152,174 control chromosomes in the GnomAD database, including 812 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 0.10 (812 hom., cov: 32)
• Consequence: SHPK NM_013276.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0540
• Publications: 3 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=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHPK	NM_013276.4	c.311-1865G>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.311-1865G>A		intron_variant	Intron 2 of 6	1	NM_013276.4	ENSP00000225519.3
ENSG00000262304	ENST00000572919.1	n.311-1865G>A		intron_variant	Intron 2 of 13	5		ENSP00000461416.1

Frequencies

GnomAD3 genomes AF: 0.100 AC: 15249 AN: 152056 Hom.: 805 Cov.: 32

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.0744

Gnomad ASJ AF: 0.144

Gnomad EAS AF: 0.00193

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.0733

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.0923

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

GnomAD4 genome AF: 0.100 AC: 15288 AN: 152174 Hom.: 812 Cov.: 32 AF XY: 0.0979 AC XY: 7281 AN XY: 74392

African (AFR) AF: 0.101 AC: 4211 AN: 41530

American (AMR) AF: 0.0743 AC: 1136 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.144 AC: 501 AN: 3470

East Asian (EAS) AF: 0.00194 AC: 10 AN: 5164

South Asian (SAS) AF: 0.121 AC: 586 AN: 4824

European-Finnish (FIN) AF: 0.0733 AC: 777 AN: 10596

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.113 AC: 7681 AN: 67990

Other (OTH) AF: 0.0919 AC: 194 AN: 2112

Alfa AF: 0.110 Hom.: 498

Bravo AF: 0.0990

Asia WGS AF: 0.0550 AC: 190 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.9
DANN	Benign	0.46
PhyloP100		-0.054
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: rs7210277; hg19: chr17-3529390;