3-43348207-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_017719.5(SNRK):ā€‹c.1948A>Gā€‹(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 (ā˜…).

Frequency

Genomes: š‘“ 0.00016 ( 0 hom., cov: 32)
Exomes š‘“: 0.00027 ( 0 hom. )

Consequence

SNRK
NM_017719.5 missense

Scores

1
18

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

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.031959146).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SNRKNM_017719.5 linkuse as main transcriptc.1948A>G p.Met650Val missense_variant 7/7 ENST00000296088.12
SNRK-AS1NR_046757.1 linkuse as main transcriptn.2187T>C non_coding_transcript_exon_variant 3/3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SNRKENST00000296088.12 linkuse as main transcriptc.1948A>G p.Met650Val missense_variant 7/71 NM_017719.5 P1Q9NRH2-1
SNRK-AS1ENST00000607513.2 linkuse as main transcriptn.706T>C non_coding_transcript_exon_variant 3/3

Frequencies

GnomAD3 genomes
AF:
0.000158
AC:
24
AN:
152182
Hom.:
0
Cov.:
32
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:
46
AN:
243524
Hom.:
0
AF XY:
0.000174
AC XY:
23
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.:
0
Cov.:
31
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:
24
AN:
152300
Hom.:
0
Cov.:
32
AF XY:
0.000148
AC XY:
11
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.:
0
Bravo
AF:
0.000155
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000241
AC:
2
ExAC
AF:
0.000199
AC:
24

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 submitterclinical testingAmbry GeneticsMay 26, 2022The 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
T
BayesDel_noAF
Benign
-0.36
CADD
Benign
13
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
D
LIST_S2
Benign
0.77
.;.;T;T
M_CAP
Benign
0.056
D
MetaRNN
Benign
0.032
T;T;T;T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
0.90
L;L;L;.
MutationTaster
Benign
0.84
D;D;D;D
PrimateAI
Benign
0.42
T
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
T
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.

Other links and lift over

dbSNP: rs202018563; hg19: chr3-43389699; COSMIC: COSV56068305; COSMIC: COSV56068305; API