chr17-3623188-T-A

Variant names:

• chr17-3623188-T-A
• rs367264
• NM_013276.4:c.647+151A>T

Variant summary

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

The NM_013276.4(SHPK):​c.647+151A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.813 in 803,732 control chromosomes in the GnomAD database, including 266,352 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 0.82 (50848 hom., cov: 31)
  • Exomes 𝑓: 0.81 (215504 hom.)
• Consequence: SHPK NM_013276.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.754
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.914 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHPK	NM_013276.4	c.647+151A>T		intron_variant	Intron 4 of 6	ENST00000225519.5	NP_037408.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SHPK	ENST00000225519.5	c.647+151A>T		intron_variant	Intron 4 of 6	1	NM_013276.4	ENSP00000225519.3
ENSG00000262304	ENST00000572919.1	n.647+151A>T		intron_variant	Intron 4 of 13	5		ENSP00000461416.1

Frequencies

GnomAD3 genomes AF: 0.816 AC: 124049 AN: 151956 Hom.: 50803 Cov.: 31

Gnomad AFR AF: 0.800

Gnomad AMI AF: 0.866

Gnomad AMR AF: 0.828

Gnomad ASJ AF: 0.823

Gnomad EAS AF: 0.935

Gnomad SAS AF: 0.770

Gnomad FIN AF: 0.839

Gnomad MID AF: 0.759

Gnomad NFE AF: 0.813

Gnomad OTH AF: 0.843

GnomAD4 exome AF: 0.812 AC: 528945 AN: 651658 Hom.: 215504 AF XY: 0.808 AC XY: 275580 AN XY: 340876

African (AFR) AF: 0.806 AC: 13813 AN: 17130

American (AMR) AF: 0.788 AC: 24148 AN: 30628

Ashkenazi Jewish (ASJ) AF: 0.816 AC: 13481 AN: 16526

East Asian (EAS) AF: 0.933 AC: 31055 AN: 33286

South Asian (SAS) AF: 0.759 AC: 44458 AN: 58606

European-Finnish (FIN) AF: 0.829 AC: 28810 AN: 34738

Middle Eastern (MID) AF: 0.728 AC: 1776 AN: 2440

European-Non Finnish (NFE) AF: 0.810 AC: 344389 AN: 425146

Other (OTH) AF: 0.815 AC: 27015 AN: 33158

GnomAD4 genome AF: 0.816 AC: 124149 AN: 152074 Hom.: 50848 Cov.: 31 AF XY: 0.816 AC XY: 60645 AN XY: 74324

African (AFR) AF: 0.800 AC: 33213 AN: 41508

American (AMR) AF: 0.828 AC: 12647 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.823 AC: 2859 AN: 3472

East Asian (EAS) AF: 0.936 AC: 4824 AN: 5152

South Asian (SAS) AF: 0.770 AC: 3709 AN: 4818

European-Finnish (FIN) AF: 0.839 AC: 8875 AN: 10580

Middle Eastern (MID) AF: 0.759 AC: 223 AN: 294

European-Non Finnish (NFE) AF: 0.813 AC: 55226 AN: 67954

Other (OTH) AF: 0.845 AC: 1787 AN: 2114

Alfa AF: 0.811 Hom.: 5829

Bravo AF: 0.818

Asia WGS AF: 0.873 AC: 3037 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.47
DANN	Benign	0.54
PhyloP100		-0.75
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs367264; hg19: chr17-3526482;