Variant 3-43347658-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP2BP4_Moderate

The NM_017719.5(SNRK):c.1399T>G(p.Leu467Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L467W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00027 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SNRK
NM_017719.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.164

Variant links:

Genes affected

SNRK (HGNC:30598): (SNF related kinase) SNRK is a member of the sucrose nonfermenting (SNF)-related kinase family of serine/threonine kinases (Kertesz et al., 2002 [PubMed 12234663]).[supplied by OMIM, Apr 2009]

SNRK links:

SNRK-AS1 (HGNC:41269): (SNRK antisense RNA 1)

SNRK-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

PP2

Missense variant where missense usually causes diseases, SNRK

BP4

Computational evidence support a benign effect (MetaRNN=0.14816976).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SNRK	NM_017719.5 linkuse as main transcript	c.1399T>G	p.Leu467Val	missense_variant	7/7	ENST00000296088.12
SNRK-AS1	NR_046757.1 linkuse as main transcript	n.2736A>C		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SNRK	ENST00000296088.12 linkuse as main transcript	c.1399T>G	p.Leu467Val	missense_variant	7/7	1	NM_017719.5	P1	Q9NRH2-1
SNRK-AS1	ENST00000607513.2 linkuse as main transcript	n.1255A>C		non_coding_transcript_exon_variant	3/3

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

151966

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000269

AC:

392

AN:

1456888

Hom.:

Cov.:

AF XY:

0.000250

AC XY:

181

AN XY:

724870

show subpopulations

Gnomad4 AFR exome

AF:

0.000240

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.0000757

Gnomad4 SAS exome

AF:

0.0000812

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000322

Gnomad4 OTH exome

AF:

0.000249

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000658

AC:

AN:

152084

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 02, 2022

The c.1399T>G (p.L467V) alteration is located in exon 7 (coding exon 5) of the SNRK gene. This alteration results from a T to G substitution at nucleotide position 1399, causing the leucine (L) at amino acid position 467 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.38

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Benign

0.075

T;T;T;.

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.55

FATHMM_MKL

Benign

0.30

M_CAP

Uncertain

0.099

MetaRNN

Benign

0.15

T;T;T;T

MetaSVM

Benign

-0.53

MutationAssessor

Benign

0.81

L;L;L;.

MutationTaster

Benign

0.73

D;D;D;D

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-0.080

N;N;N;N

REVEL

Benign

0.19

Sift

Benign

0.18

T;T;T;T

Sift4G

Benign

0.37

T;T;T;T

Polyphen

1.0

D;D;D;.

Vest4

0.48

MutPred

0.22

Gain of glycosylation at S472 (P = 0.0157);Gain of glycosylation at S472 (P = 0.0157);Gain of glycosylation at S472 (P = 0.0157);.;

MVP

0.44

MPC

1.5

ClinPred

0.42

GERP RS

-2.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.056

gMVP

0.24

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