Variant 17-3623343-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_013276.4(SHPK):c.643G>A(p.Glu215Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 1,613,856 control chromosomes in the GnomAD database, including 19,206 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.20 ( 4854 hom., cov: 33)

Exomes 𝑓: 0.12 ( 14352 hom. )

Consequence

SHPK
NM_013276.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.47

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0061131716).

BP6

Variant 17-3623343-C-T is Benign according to our data. Variant chr17-3623343-C-T is described in ClinVar as [Benign]. Clinvar id is 1166170.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.431 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SHPK	NM_013276.4 linkuse as main transcript	c.643G>A	p.Glu215Lys	missense_variant	4/7	ENST00000225519.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SHPK	ENST00000225519.5 linkuse as main transcript	c.643G>A	p.Glu215Lys	missense_variant	4/7	1	NM_013276.4	P1

Frequencies

GnomAD3 genomes

AF:

0.204

AC:

31085

AN:

152032

Hom.:

4835

Cov.:

show subpopulations

Gnomad AFR

AF:

0.436

Gnomad AMI

AF:

0.120

Gnomad AMR

AF:

0.155

Gnomad ASJ

AF:

0.0810

Gnomad EAS

AF:

0.219

Gnomad SAS

AF:

0.227

Gnomad FIN

AF:

0.0756

Gnomad MID

AF:

0.133

Gnomad NFE

AF:

0.101

Gnomad OTH

AF:

0.171

GnomAD3 exomes

AF:

0.151

AC:

37890

AN:

251358

Hom.:

4050

AF XY:

0.147

AC XY:

19980

AN XY:

135864

show subpopulations

Gnomad AFR exome

AF:

0.446

Gnomad AMR exome

AF:

0.143

Gnomad ASJ exome

AF:

0.0807

Gnomad EAS exome

AF:

0.227

Gnomad SAS exome

AF:

0.223

Gnomad FIN exome

AF:

0.0804

Gnomad NFE exome

AF:

0.100

Gnomad OTH exome

AF:

0.124

GnomAD4 exome

AF:

0.122

AC:

178037

AN:

1461708

Hom.:

14352

Cov.:

AF XY:

0.123

AC XY:

89142

AN XY:

727172

show subpopulations

Gnomad4 AFR exome

AF:

0.460

Gnomad4 AMR exome

AF:

0.145

Gnomad4 ASJ exome

AF:

0.0826

Gnomad4 EAS exome

AF:

0.218

Gnomad4 SAS exome

AF:

0.215

Gnomad4 FIN exome

AF:

0.0820

Gnomad4 NFE exome

AF:

0.102

Gnomad4 OTH exome

AF:

0.140

GnomAD4 genome

AF:

0.205

AC:

31157

AN:

152148

Hom.:

4854

Cov.:

AF XY:

0.203

AC XY:

15113

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.436

Gnomad4 AMR

AF:

0.155

Gnomad4 ASJ

AF:

0.0810

Gnomad4 EAS

AF:

0.220

Gnomad4 SAS

AF:

0.227

Gnomad4 FIN

AF:

0.0756

Gnomad4 NFE

AF:

0.101

Gnomad4 OTH

AF:

0.179

Alfa

AF:

0.118

Hom.:

3771

Bravo

AF:

0.222

TwinsUK

AF:

0.100

AC:

371

ALSPAC

AF:

0.106

AC:

409

ESP6500AA

AF:

0.434

AC:

1912

ESP6500EA

AF:

0.0967

AC:

832

ExAC

AF:

0.158

AC:

19164

Asia WGS

AF:

0.312

AC:

1088

AN:

3478

EpiCase

AF:

0.0920

EpiControl

AF:

0.0933

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Uncertain

1.0

Eigen

Benign

-0.065

Eigen_PC

Benign

-0.035

FATHMM_MKL

Uncertain

0.92

MetaRNN

Benign

0.0061

MetaSVM

Benign

-0.87

MutationTaster

Benign

0.80

PrimateAI

Benign

0.45

PROVEAN

Benign

-2.1

REVEL

Benign

0.077

Sift

Benign

0.030

Sift4G

Benign

0.089

Vest4

0.13

MPC

0.45

ClinPred

0.021

GERP RS

4.1

gMVP

0.54

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over