3-43348414-G-A

Position:

• chr3-43348414-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_017719.5(SNRK):​c.2155G>A​(p.Glu719Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict 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: 2.27

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15949848).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SNRK	NM_017719.5	c.2155G>A	p.Glu719Lys	missense_variant	7/7	ENST00000296088.12
SNRK-AS1	NR_046757.1	n.1980C>T		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SNRK	ENST00000296088.12	c.2155G>A	p.Glu719Lys	missense_variant	7/7	1	NM_017719.5	P1
SNRK-AS1	ENST00000607513.2	n.607-108C>T		intron_variant, non_coding_transcript_variant

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 01, 2023

The c.2155G>A (p.E719K) alteration is located in exon 7 (coding exon 5) of the SNRK gene. This alteration results from a G to A substitution at nucleotide position 2155, causing the glutamic acid (E) at amino acid position 719 to be replaced by a lysine (K). 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	0.13
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.052	T;T;T;.
Eigen	Benign	-0.12
Eigen_PC	Benign	0.015
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.88	.;.;D;D
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.16	T;T;T;T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	0.55	N;N;N;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Benign	0.42	T
PROVEAN	Benign	0.070	N;N;N;N
REVEL	Benign	0.083
Sift	Benign	0.047	D;D;D;D
Sift4G	Benign	0.67	T;T;T;T
Polyphen		0.079	B;B;B;.
Vest4		0.21
MutPred		0.28		Gain of MoRF binding (P = 0.0075);Gain of MoRF binding (P = 0.0075);Gain of MoRF binding (P = 0.0075);.;
MVP		0.48
MPC		0.64
ClinPred		0.39	T
GERP RS		5.4
Varity_R		0.093
gMVP		0.15

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: chr3-43389906;