3-9757579-G-T

Variant names:

• chr3-9757579-G-T
• rs757567412
• NM_003656.5:c.1073C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003656.5(CAMK1):​c.1073C>A​(p.Pro358Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,838 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict 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. P358L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CAMK1 NM_003656.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.844
• Publications: 0 publications found

Genes affected

CAMK1 (HGNC:1459): (calcium/calmodulin dependent protein kinase I) Calcium/calmodulin-dependent protein kinase I is expressed in many tissues and is a component of a calmodulin-dependent protein kinase cascade. Calcium/calmodulin directly activates calcium/calmodulin-dependent protein kinase I by binding to the enzyme and indirectly promotes the phosphorylation and synergistic activation of the enzyme by calcium/calmodulin-dependent protein kinase I kinase. [provided by RefSeq, Jul 2008]

OGG1 (HGNC:8125): (8-oxoguanine DNA glycosylase) This gene encodes the enzyme responsible for the excision of 8-oxoguanine, a mutagenic base byproduct which occurs as a result of exposure to reactive oxygen. The action of this enzyme includes lyase activity for chain cleavage. Alternative splicing of the C-terminal region of this gene classifies splice variants into two major groups, type 1 and type 2, depending on the last exon of the sequence. Type 1 alternative splice variants end with exon 7 and type 2 end with exon 8. All variants share the N-terminal region in common, which contains a mitochondrial targeting signal that is essential for mitochondrial localization. Many alternative splice variants for this gene have been described, but the full-length nature for every variant has not been determined. [provided by RefSeq, Aug 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.075319946).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003656.5. 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
	CAMK1	NM_003656.5	MANE Select	c.1073C>A	p.Pro358Gln	missense	Exon 12 of 12	NP_003647.1	B0YIY3
	OGG1	NM_016821.3		c.948+763G>T		intron	N/A	NP_058214.1	O15527-4
	OGG1	NM_016826.3		c.747+2694G>T		intron	N/A	NP_058434.1	E5KPM6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAMK1	ENST00000256460.8	TSL:1 MANE Select	c.1073C>A	p.Pro358Gln	missense	Exon 12 of 12	ENSP00000256460.3	Q14012
	OGG1	ENST00000302036.12	TSL:1	c.948+763G>T		intron	N/A	ENSP00000306561.7	O15527-4
	OGG1	ENST00000352937.6	TSL:1	c.747+2694G>T		intron	N/A	ENSP00000344899.6	H7BXZ1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461838 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727224

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53396

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112004

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.069	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	18
DANN	Benign	0.97
DEOGEN2	Benign	0.10	T
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.28
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.075	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.84
PrimateAI	Benign	0.39	T
PROVEAN	Benign	0.27	N
REVEL	Benign	0.050
Sift	Uncertain	0.0060	D
Sift4G	Benign	0.14	T
Polyphen		0.0010	B
Vest4		0.26
MutPred		0.27		Gain of solvent accessibility (P = 0.0202)
MVP		0.65
MPC		0.19
ClinPred		0.30	T
GERP RS		3.8
Varity_R		0.050
gMVP		0.43
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs757567412; hg19: chr3-9799263;