chr3-43348156-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.1897A>Gā€‹(p.Met633Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000259 in 1,583,040 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‘“ 0.000026 ( 0 hom., cov: 33)
Exomes š‘“: 0.000026 ( 0 hom. )

Consequence

SNRK
NM_017719.5 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.206
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=0.011000633).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SNRKNM_017719.5 linkuse as main transcriptc.1897A>G p.Met633Val missense_variant 7/7 ENST00000296088.12 NP_060189.3
SNRK-AS1NR_046757.1 linkuse as main transcriptn.2238T>C non_coding_transcript_exon_variant 3/3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SNRKENST00000296088.12 linkuse as main transcriptc.1897A>G p.Met633Val missense_variant 7/71 NM_017719.5 ENSP00000296088 P1Q9NRH2-1
SNRK-AS1ENST00000607513.2 linkuse as main transcriptn.757T>C non_coding_transcript_exon_variant 3/3

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152196
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
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:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000500
AC:
11
AN:
219956
Hom.:
0
AF XY:
0.0000504
AC XY:
6
AN XY:
119152
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000669
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000580
Gnomad SAS exome
AF:
0.000200
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000198
Gnomad OTH exome
AF:
0.000194
GnomAD4 exome
AF:
0.0000259
AC:
37
AN:
1430726
Hom.:
0
Cov.:
31
AF XY:
0.0000324
AC XY:
23
AN XY:
709366
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000250
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000253
Gnomad4 SAS exome
AF:
0.000246
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000109
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152314
Hom.:
0
Cov.:
33
AF XY:
0.0000134
AC XY:
1
AN XY:
74476
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000653
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000493
Hom.:
0
Bravo
AF:
0.0000264
ExAC
AF:
0.0000331
AC:
4

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 GeneticsMar 07, 2023The c.1897A>G (p.M633V) 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 1897, causing the methionine (M) at amino acid position 633 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
0.056
BayesDel_addAF
Benign
-0.50
T
BayesDel_noAF
Benign
-0.67
CADD
Benign
6.9
DANN
Benign
0.67
DEOGEN2
Benign
0.034
T;T;T;.
Eigen
Benign
-1.3
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.071
N
LIST_S2
Benign
0.60
.;.;T;T
M_CAP
Benign
0.044
D
MetaRNN
Benign
0.011
T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
-0.34
N;N;N;.
MutationTaster
Benign
1.0
N;N;N;N
PrimateAI
Benign
0.45
T
PROVEAN
Benign
-0.070
N;N;N;N
REVEL
Benign
0.038
Sift
Benign
0.43
T;T;T;T
Sift4G
Benign
1.0
T;T;T;T
Polyphen
0.0
B;B;B;.
Vest4
0.046
MVP
0.31
MPC
0.57
ClinPred
0.027
T
GERP RS
-5.7
Varity_R
0.044
gMVP
0.30

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: rs200446000; hg19: chr3-43389648; API