1-20485358-C-T

Variant names:

• chr1-20485358-C-T
• rs773958625
• NM_018584.6:c.22G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018584.6(CAMK2N1):​c.22G>A​(p.Gly8Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000148 in 1,347,776 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G8R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: CAMK2N1 NM_018584.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.40

Genes affected

CAMK2N1 (HGNC:24190): (calcium/calmodulin dependent protein kinase II inhibitor 1) Enables calcium-dependent protein kinase inhibitor activity and protein kinase binding activity. Involved in several processes, including negative regulation of ERK1 and ERK2 cascade; negative regulation of cell population proliferation; and negative regulation of cellular protein metabolic process. Predicted to be located in synapse. Implicated in ovarian cancer; ovarian carcinoma; and prostate adenocarcinoma. Biomarker of hepatocellular carcinoma; oral squamous cell carcinoma; prostate cancer; and thyroid gland papillary carcinoma. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.058293402).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAMK2N1	NM_018584.6	c.22G>A	p.Gly8Ser	missense_variant	Exon 1 of 2	ENST00000375078.4	NP_061054.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAMK2N1	ENST00000375078.4	c.22G>A	p.Gly8Ser	missense_variant	Exon 1 of 2	1	NM_018584.6	ENSP00000364219.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000148 AC: 2 AN: 1347776 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 661936

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: 9.47e-7

Gnomad4 OTH exome AF: 0.0000181

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.60
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.015	T
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.28
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.82	T
M_CAP	Uncertain	0.28	D
MetaRNN	Benign	0.058	T
MetaSVM	Benign	-1.0	T
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.058
Sift	Benign	0.66	T
Sift4G	Benign	0.54	T
Polyphen		0.0020	B
Vest4		0.089
MutPred		0.15		Gain of phosphorylation at G8 (P = 0.0294);
MVP		0.030
MPC		1.1
ClinPred		0.93	D
GERP RS		1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.14
gMVP		0.18

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs773958625; hg19: chr1-20811851;