NM_017719.5:c.1399T>G

Variant names:

• chr3-43347658-T-G
• rs2091287853
• NM_017719.5:c.1399T>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_017719.5(SNRK):​c.1399T>G​(p.Leu467Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L467W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00027 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SNRK NM_017719.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.164
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.14816976).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017719.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNRK	NM_017719.5	MANE Select	c.1399T>G	p.Leu467Val	missense	Exon 7 of 7	NP_060189.3
	SNRK	NM_001100594.2		c.1399T>G	p.Leu467Val	missense	Exon 6 of 6	NP_001094064.1	Q9NRH2-1
	SNRK	NM_001330750.2		c.781T>G	p.Leu261Val	missense	Exon 5 of 5	NP_001317679.1	E7EUC4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNRK	ENST00000296088.12	TSL:1 MANE Select	c.1399T>G	p.Leu467Val	missense	Exon 7 of 7	ENSP00000296088.7	Q9NRH2-1
	SNRK	ENST00000429705.6	TSL:1	c.1399T>G	p.Leu467Val	missense	Exon 6 of 6	ENSP00000411375.2	Q9NRH2-1
	SNRK	ENST00000454177.5	TSL:2	c.1399T>G	p.Leu467Val	missense	Exon 8 of 8	ENSP00000401246.1	Q9NRH2-1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151966 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000269 AC: 392 AN: 1456888 Hom.: 0 Cov.: 31 AF XY: 0.000250 AC XY: 181 AN XY: 724870

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000240 AC: 8 AN: 33402

American (AMR) AF: 0.0000224 AC: 1 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26108

East Asian (EAS) AF: 0.0000757 AC: 3 AN: 39652

South Asian (SAS) AF: 0.0000812 AC: 7 AN: 86164

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53044

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 0.000322 AC: 357 AN: 1107826

Other (OTH) AF: 0.000249 AC: 15 AN: 60228

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000658 AC: 1 AN: 152084 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74338

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 41508

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5160

South Asian (SAS) AF: 0.00 AC: 0 AN: 4804

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10580

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67958

Other (OTH) AF: 0.00 AC: 0 AN: 2112

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.075	T
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.55
FATHMM_MKL	Benign	0.30	N
LIST_S2	Uncertain	0.90	D
M_CAP	Uncertain	0.099	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.53	T
MutationAssessor	Benign	0.81	L
PhyloP100		-0.16
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-0.080	N
REVEL	Benign	0.19
Sift	Benign	0.18	T
Sift4G	Benign	0.37	T
Polyphen		1.0	D
Vest4		0.48
MutPred		0.22		Gain of glycosylation at S472 (P = 0.0157)
MVP		0.44
MPC		1.5
ClinPred		0.42	T
GERP RS		-2.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.056
gMVP		0.24
Mutation Taster		=64/36	polymorphism

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

Other links and lift over

dbSNP: rs2091287853; hg19: chr3-43389150;