3-43303326-G-T

Variant names:

• chr3-43303326-G-T
• rs2090912306
• NM_017719.5:c.123G>T

Variant summary

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

The NM_017719.5(SNRK):​c.123G>T​(p.Lys41Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,840 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: SNRK NM_017719.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.843

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNRK	NM_017719.5	c.123G>T	p.Lys41Asn	missense_variant	Exon 3 of 7	ENST00000296088.12	NP_060189.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SNRK	ENST00000296088.12	c.123G>T	p.Lys41Asn	missense_variant	Exon 3 of 7	1	NM_017719.5	ENSP00000296088.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461840 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727214

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000360

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 25, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.123G>T (p.K41N) alteration is located in exon 3 (coding exon 1) of the SNRK gene. This alteration results from a G to T substitution at nucleotide position 123, causing the lysine (K) at amino acid position 41 to be replaced by an asparagine (N). 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	Pathogenic	0.91
BayesDel_addAF	Benign	-0.044	T
BayesDel_noAF	Benign	-0.30
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T;T;T
Eigen	Benign	-0.095
Eigen_PC	Benign	-0.095
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.94	.;.;D
M_CAP	Uncertain	0.11	D
MetaRNN	Uncertain	0.69	D;D;D
MetaSVM	Benign	-0.61	T
MutationAssessor	Benign	1.7	L;L;L
PrimateAI	Pathogenic	0.89	D
PROVEAN	Uncertain	-4.1	D;D;D
REVEL	Benign	0.24
Sift	Uncertain	0.0020	D;D;D
Sift4G	Uncertain	0.013	D;D;D
Polyphen		1.0	D;D;D
Vest4		0.65
MutPred		0.60		Loss of methylation at K41 (P = 0.0315);Loss of methylation at K41 (P = 0.0315);Loss of methylation at K41 (P = 0.0315);
MVP		0.79
MPC		3.0
ClinPred		0.98	D
GERP RS		0.14
Varity_R		0.92
gMVP		0.95

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

LitVar

Other links and lift over

dbSNP: rs2090912306; hg19: chr3-43344818;