chr3-43303762-C-A

Variant names:

• chr3-43303762-C-A
• rs2090914990
• NM_017719.5:c.559C>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_017719.5(SNRK):​c.559C>A​(p.Leu187Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,282 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: SNRK NM_017719.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.91

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNRK	NM_017719.5	c.559C>A	p.Leu187Ile	missense_variant	Exon 3 of 7	ENST00000296088.12	NP_060189.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SNRK	ENST00000296088.12	c.559C>A	p.Leu187Ile	missense_variant	Exon 3 of 7	1	NM_017719.5	ENSP00000296088.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461282 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726922

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 25, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.559C>A (p.L187I) alteration is located in exon 3 (coding exon 1) of the SNRK gene. This alteration results from a C to A substitution at nucleotide position 559, causing the leucine (L) at amino acid position 187 to be replaced by an isoleucine (I). 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	Pathogenic	0.97
BayesDel_addAF	Uncertain	0.070	D
BayesDel_noAF	Benign	-0.14
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.083	T;T;T
Eigen	Uncertain	0.67
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	.;.;D
M_CAP	Benign	0.038	D
MetaRNN	Uncertain	0.47	T;T;T
MetaSVM	Benign	-0.29	T
MutationAssessor	Benign	0.61	N;N;N
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-1.9	N;N;N
REVEL	Benign	0.21
Sift	Benign	0.050	D;D;D
Sift4G	Uncertain	0.048	D;D;D
Polyphen		1.0	D;D;D
Vest4		0.43
MutPred		0.55		Gain of glycosylation at Y191 (P = 0.0062);Gain of glycosylation at Y191 (P = 0.0062);Gain of glycosylation at Y191 (P = 0.0062);
MVP		0.63
MPC		2.8
ClinPred		0.95	D
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.40
gMVP		0.60

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

Other links and lift over

dbSNP: rs2090914990; hg19: chr3-43345254;