chr3-43347721-C-G

Variant names:

• chr3-43347721-C-G
• NM_017719.5:c.1462C>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_017719.5(SNRK):​c.1462C>G​(p.Gln488Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SNRK NM_017719.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.77

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)

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.41250014).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNRK	NM_017719.5	c.1462C>G	p.Gln488Glu	missense_variant	Exon 7 of 7	ENST00000296088.12	NP_060189.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SNRK	ENST00000296088.12	c.1462C>G	p.Gln488Glu	missense_variant	Exon 7 of 7	1	NM_017719.5	ENSP00000296088.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 26, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1462C>G (p.Q488E) alteration is located in exon 7 (coding exon 5) of the SNRK gene. This alteration results from a C to G substitution at nucleotide position 1462, causing the glutamine (Q) at amino acid position 488 to be replaced by a glutamic acid (E). 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	0.29
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.059	T;T;T;.
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.90	.;.;D;D
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.41	T;T;T;T
MetaSVM	Benign	-0.79	T
MutationAssessor	Benign	0.81	L;L;L;.
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	0.080	N;N;N;N
REVEL	Benign	0.18
Sift	Benign	0.15	T;T;T;T
Sift4G	Benign	0.77	T;T;T;T
Polyphen		0.90	P;P;P;.
Vest4		0.72
MutPred		0.28		Gain of catalytic residue at Q488 (P = 0.0702);Gain of catalytic residue at Q488 (P = 0.0702);Gain of catalytic residue at Q488 (P = 0.0702);.;
MVP		0.77
MPC		0.63
ClinPred		0.80	D
GERP RS		4.8
Varity_R		0.29
gMVP		0.55

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-43389213;