Variant 3-43348207-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PM2PP2BP4_Strong

The NM_017719.5(SNRK):c.1948A>G(p.Met650Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00026 in 1,608,536 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00027 ( 0 hom. )

Consequence

SNRK
NM_017719.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.34

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.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant where missense usually causes diseases, SNRK

BP4

Computational evidence support a benign effect (MetaRNN=0.031959146).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SNRK	NM_017719.5 linkuse as main transcript	c.1948A>G	p.Met650Val	missense_variant	7/7	ENST00000296088.12
SNRK-AS1	NR_046757.1 linkuse as main transcript	n.2187T>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.1948A>G	p.Met650Val	missense_variant	7/7	1	NM_017719.5	P1	Q9NRH2-1
SNRK-AS1	ENST00000607513.2 linkuse as main transcript	n.706T>C		non_coding_transcript_exon_variant	3/3

Frequencies

GnomAD3 genomes

AF:

0.000158

AC:

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000771

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000250

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000189

AC:

AN:

243524

Hom.:

AF XY:

0.000174

AC XY:

AN XY:

132234

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000119

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000560

Gnomad SAS exome

AF:

0.0000673

Gnomad FIN exome

AF:

0.000283

Gnomad NFE exome

AF:

0.000208

Gnomad OTH exome

AF:

0.000171

GnomAD4 exome

AF:

0.000271

AC:

394

AN:

1456236

Hom.:

Cov.:

AF XY:

0.000265

AC XY:

192

AN XY:

724322

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000911

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000605

Gnomad4 SAS exome

AF:

0.0000585

Gnomad4 FIN exome

AF:

0.000320

Gnomad4 NFE exome

AF:

0.000297

Gnomad4 OTH exome

AF:

0.000250

GnomAD4 genome

AF:

0.000158

AC:

AN:

152300

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000773

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.000250

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000273

Hom.:

Bravo

AF:

0.000155

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000241

AC:

ExAC

AF:

0.000199

AC:

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

May 26, 2022

The c.1948A>G (p.M650V) alteration is located in exon 7 (coding exon 5) of the SNRK gene. This alteration results from a A to G substitution at nucleotide position 1948, causing the methionine (M) at amino acid position 650 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

0.11

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.36

Cadd

Benign

Dann

Benign

0.91

DEOGEN2

Benign

0.053

T;T;T;.

Eigen

Benign

-0.47

Eigen_PC

Benign

-0.33

FATHMM_MKL

Uncertain

0.89

M_CAP

Benign

0.056

MetaRNN

Benign

0.032

T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.90

L;L;L;.

MutationTaster

Benign

0.84

D;D;D;D

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.59

N;N;N;N

REVEL

Benign

0.14

Sift

Benign

0.29

T;T;T;T

Sift4G

Benign

0.32

T;T;T;T

Polyphen

0.0

B;B;B;.

Vest4

0.18

MVP

0.29

MPC

0.57

ClinPred

0.014

GERP RS

0.61

Varity_R

0.12

gMVP

0.47

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