Variant 3-43347529-C-T 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.1270C>T(p.Leu424Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000744 in 1,613,476 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

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

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

SNRK
NM_017719.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.21

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=0.03864196).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SNRK	NM_017719.5 linkuse as main transcript	c.1270C>T	p.Leu424Phe	missense_variant	7/7	ENST00000296088.12
SNRK-AS1	NR_046757.1 linkuse as main transcript	n.2865G>A		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.1270C>T	p.Leu424Phe	missense_variant	7/7	1	NM_017719.5	P1	Q9NRH2-1
SNRK-AS1	ENST00000607513.2 linkuse as main transcript	n.1384G>A		non_coding_transcript_exon_variant	3/3

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152076

Hom.:

Cov.:

show subpopulations

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:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000282

AC:

AN:

247796

Hom.:

AF XY:

0.0000297

AC XY:

AN XY:

134546

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000230

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000753

AC:

AN:

1461282

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

726908

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000928

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152194

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74412

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:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000331

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Aug 04, 2023

The c.1270C>T (p.L424F) alteration is located in exon 7 (coding exon 5) of the SNRK gene. This alteration results from a C to T substitution at nucleotide position 1270, causing the leucine (L) at amino acid position 424 to be replaced by a phenylalanine (F). 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

0.061

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.47

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Benign

0.044

T;T;T;.

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.46

M_CAP

Benign

0.048

MetaRNN

Benign

0.039

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;N;N;.

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-0.71

N;N;N;N

REVEL

Benign

0.034

Sift

Uncertain

0.024

D;D;D;D

Sift4G

Benign

0.59

T;T;T;T

Polyphen

0.66

P;P;P;.

Vest4

0.16

MutPred

0.37

Loss of glycosylation at P429 (P = 0.042);Loss of glycosylation at P429 (P = 0.042);Loss of glycosylation at P429 (P = 0.042);.;

MVP

0.29

MPC

0.69

ClinPred

0.037

GERP RS

1.7

Varity_R

0.070

gMVP

0.10

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