Variant 17-3610760-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_013276.4(SHPK):c.1237A>G(p.Met413Val) variant causes a missense change. The variant allele was found at a frequency of 0.00543 in 1,614,056 control chromosomes in the GnomAD database, including 40 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0050 ( 7 hom., cov: 33)

Exomes 𝑓: 0.0055 ( 33 hom. )

Consequence

SHPK
NM_013276.4 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 7.00

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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010470659).

BP6

Variant 17-3610760-T-C is Benign according to our data. Variant chr17-3610760-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 786430.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SHPK	NM_013276.4 linkuse as main transcript	c.1237A>G	p.Met413Val	missense_variant	7/7	ENST00000225519.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SHPK	ENST00000225519.5 linkuse as main transcript	c.1237A>G	p.Met413Val	missense_variant	7/7	1	NM_013276.4	P1

Frequencies

GnomAD3 genomes

AF:

0.00497

AC:

756

AN:

152124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00130

Gnomad AMI

AF:

0.0384

Gnomad AMR

AF:

0.00249

Gnomad ASJ

AF:

0.00691

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00349

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00822

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00427

AC:

1074

AN:

251282

Hom.:

AF XY:

0.00417

AC XY:

566

AN XY:

135806

show subpopulations

Gnomad AFR exome

AF:

0.000738

Gnomad AMR exome

AF:

0.00173

Gnomad ASJ exome

AF:

0.00824

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00264

Gnomad NFE exome

AF:

0.00730

Gnomad OTH exome

AF:

0.00490

GnomAD4 exome

AF:

0.00548

AC:

8004

AN:

1461814

Hom.:

Cov.:

AF XY:

0.00530

AC XY:

3853

AN XY:

727204

show subpopulations

Gnomad4 AFR exome

AF:

0.000777

Gnomad4 AMR exome

AF:

0.00203

Gnomad4 ASJ exome

AF:

0.00750

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000151

Gnomad4 FIN exome

AF:

0.00320

Gnomad4 NFE exome

AF:

0.00647

Gnomad4 OTH exome

AF:

0.00480

GnomAD4 genome

AF:

0.00496

AC:

755

AN:

152242

Hom.:

Cov.:

AF XY:

0.00466

AC XY:

347

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.00130

Gnomad4 AMR

AF:

0.00248

Gnomad4 ASJ

AF:

0.00691

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00349

Gnomad4 NFE

AF:

0.00822

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00614

Hom.:

Bravo

AF:

0.00468

TwinsUK

AF:

0.00701

AC:

ALSPAC

AF:

0.00727

AC:

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00872

AC:

ExAC

AF:

0.00442

AC:

537

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.00774

EpiControl

AF:

0.00711

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jun 01, 2022	SHPK: BS2 -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 22, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.27

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Uncertain

0.030

CADD

Benign

DANN

Uncertain

1.0

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.41

FATHMM_MKL

Pathogenic

0.98

M_CAP

Benign

0.030

MetaRNN

Benign

0.010

MetaSVM

Benign

-0.93

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.50

PROVEAN

Uncertain

-2.8

REVEL

Uncertain

0.32

Sift

Uncertain

0.0070

Sift4G

Uncertain

0.0090

Vest4

0.74

MVP

0.23

MPC

0.85

ClinPred

0.019

GERP RS

4.9

gMVP

0.74

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