rs2125651199

Variant names:

• chr3-43347659-T-G
• rs2125651199
• NM_017719.5:c.1400T>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_017719.5(SNRK):​c.1400T>G​(p.Leu467Trp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. L467V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.00015 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SNRK NM_017719.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.95
• 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: Uncertain_significance. The variant received 2 ACMG points.

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

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.1400T>G	p.Leu467Trp	missense	Exon 7 of 7	NP_060189.3
	SNRK	NM_001100594.2		c.1400T>G	p.Leu467Trp	missense	Exon 6 of 6	NP_001094064.1	Q9NRH2-1
	SNRK	NM_001330750.2		c.782T>G	p.Leu261Trp	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.1400T>G	p.Leu467Trp	missense	Exon 7 of 7	ENSP00000296088.7	Q9NRH2-1
	SNRK	ENST00000429705.6	TSL:1	c.1400T>G	p.Leu467Trp	missense	Exon 6 of 6	ENSP00000411375.2	Q9NRH2-1
	SNRK	ENST00000454177.5	TSL:2	c.1400T>G	p.Leu467Trp	missense	Exon 8 of 8	ENSP00000401246.1	Q9NRH2-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000154 AC: 225 AN: 1458500 Hom.: 0 Cov.: 31 AF XY: 0.000134 AC XY: 97 AN XY: 725614

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

African (AFR) AF: 0.000179 AC: 6 AN: 33436

American (AMR) AF: 0.0000224 AC: 1 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26118

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39682

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86188

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53078

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.000185 AC: 205 AN: 1109240

Other (OTH) AF: 0.000133 AC: 8 AN: 60282

⚠️ 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 Cov.: 32

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	Uncertain	0.50
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Pathogenic	27
DANN	Benign	0.96
DEOGEN2	Benign	0.097	T
Eigen	Uncertain	0.65
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.87	D
M_CAP	Uncertain	0.15	D
MetaRNN	Uncertain	0.51	D
MetaSVM	Uncertain	-0.23	T
MutationAssessor	Benign	0.81	L
PhyloP100		8.0
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-1.1	N
REVEL	Uncertain	0.32
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.080	T
Polyphen		1.0	D
Vest4		0.65
MutPred		0.35		Gain of glycosylation at S472 (P = 0.0157)
MVP		0.64
MPC		1.9
ClinPred		0.75	D
GERP RS		4.8
Varity_R		0.39
gMVP		0.41
Mutation Taster		=36/64	disease causing

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: rs2125651199; hg19: chr3-43389151;