10-73814020-A-T

Position:

• chr10-73814020-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001367534.1(CAMK2G):​c.*498T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 152,496 control chromosomes in the GnomAD database, including 1,356 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.13 (1356 hom., cov: 32)
  • Exomes 𝑓: 0.15 (0 hom.)
• Consequence: CAMK2G NM_001367534.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.30

Genes affected

CAMK2G (HGNC:1463): (calcium/calmodulin dependent protein kinase II gamma) The product of this gene is one of the four subunits of an enzyme which belongs to the serine/threonine protein kinase family, and to the Ca(2+)/calmodulin-dependent protein kinase subfamily. Calcium signaling is crucial for several aspects of plasticity at glutamatergic synapses. In mammalian cells the enzyme is composed of four different chains: alpha, beta, gamma, and delta. The product of this gene is a gamma chain. Many alternatively spliced transcripts encoding different isoforms have been described but the full-length nature of all the variants has not been determined.[provided by RefSeq, Mar 2011]

CAMK2G-AS1 (HGNC:56057): (CAMK2G antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.183 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAMK2G	NM_001367534.1	c.*498T>A		3_prime_UTR_variant	23/23	ENST00000423381.6	NP_001354463.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAMK2G	ENST00000423381.6	c.*498T>A		3_prime_UTR_variant	23/23	5	NM_001367534.1	ENSP00000410298
CAMK2G-AS1	ENST00000434147.1	n.136+367A>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19569 AN: 152070 Hom.: 1341 Cov.: 32

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.210

Gnomad EAS AF: 0.125

Gnomad SAS AF: 0.193

Gnomad FIN AF: 0.133

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.132

Gnomad OTH AF: 0.125

GnomAD4 exome AF: 0.149 AC: 46 AN: 308 Hom.: 0 Cov.: 0 AF XY: 0.153 AC XY: 30 AN XY: 196

Gnomad4 AFR exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.151

Gnomad4 NFE exome AF: 0.250

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.129 AC: 19617 AN: 152188 Hom.: 1356 Cov.: 32 AF XY: 0.129 AC XY: 9563 AN XY: 74410

Gnomad4 AFR AF: 0.117

Gnomad4 AMR AF: 0.102

Gnomad4 ASJ AF: 0.210

Gnomad4 EAS AF: 0.125

Gnomad4 SAS AF: 0.193

Gnomad4 FIN AF: 0.133

Gnomad4 NFE AF: 0.132

Gnomad4 OTH AF: 0.123

Alfa AF: 0.135 Hom.: 196

Bravo AF: 0.127

Asia WGS AF: 0.149 AC: 520 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	12
DANN	Benign	0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs2306327; hg19: chr10-75573778;