3-43348171-C-T

Variant names:

• chr3-43348171-C-T
• rs772911877
• NM_017719.5:c.1912C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_017719.5(SNRK):​c.1912C>T​(p.Arg638Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000189 in 1,588,094 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000020 (0 hom.)
• Consequence: SNRK NM_017719.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.700
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30506945).

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.1912C>T	p.Arg638Cys	missense	Exon 7 of 7	NP_060189.3
	SNRK	NM_001100594.2		c.1912C>T	p.Arg638Cys	missense	Exon 6 of 6	NP_001094064.1	Q9NRH2-1
	SNRK	NM_001330750.2		c.1294C>T	p.Arg432Cys	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.1912C>T	p.Arg638Cys	missense	Exon 7 of 7	ENSP00000296088.7	Q9NRH2-1
	SNRK	ENST00000429705.6	TSL:1	c.1912C>T	p.Arg638Cys	missense	Exon 6 of 6	ENSP00000411375.2	Q9NRH2-1
	SNRK	ENST00000454177.5	TSL:2	c.1912C>T	p.Arg638Cys	missense	Exon 8 of 8	ENSP00000401246.1	Q9NRH2-1

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152218 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000134 AC: 3 AN: 223914 AF XY: 0.0000247

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000499

Gnomad NFE exome AF: 0.0000195

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000195 AC: 28 AN: 1435876 Hom.: 0 Cov.: 31 AF XY: 0.0000168 AC XY: 12 AN XY: 712526

African (AFR) AF: 0.00 AC: 0 AN: 32606

American (AMR) AF: 0.00 AC: 0 AN: 40678

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23768

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39552

South Asian (SAS) AF: 0.0000488 AC: 4 AN: 81984

European-Finnish (FIN) AF: 0.0000573 AC: 3 AN: 52364

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5542

European-Non Finnish (NFE) AF: 0.0000173 AC: 19 AN: 1100260

Other (OTH) AF: 0.0000169 AC: 1 AN: 59122

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152218 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74370

African (AFR) AF: 0.0000241 AC: 1 AN: 41468

American (AMR) AF: 0.00 AC: 0 AN: 15290

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.0000604 Hom.: 0

Bravo AF: 0.0000189

ExAC AF: 0.0000165 AC: 2

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	0.14
BayesDel_addAF	Benign	0.0018	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.063	T
Eigen	Benign	0.014
Eigen_PC	Benign	0.0073
FATHMM_MKL	Benign	0.71	D
LIST_S2	Uncertain	0.93	D
M_CAP	Uncertain	0.27	D
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-0.73	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.70
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.19
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.013	D
Polyphen		0.97	D
Vest4		0.47
MutPred		0.52		Loss of helix (P = 0.0093)
MVP		0.55
MPC		1.3
ClinPred		0.58	D
GERP RS		4.5
Varity_R		0.16
gMVP		0.31
Mutation Taster		=90/10	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: rs772911877; hg19: chr3-43389663; COSMIC: COSV56070513; COSMIC: COSV56070513;