17-4980523-C-T

Position:

• chr17-4980523-C-T

Variant summary

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

The NM_015099.4(CAMTA2):​c.799G>A​(p.Ala267Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,457,038 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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. A267P) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 19)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: CAMTA2 NM_015099.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.379

Genes affected

CAMTA2 (HGNC:18807): (calmodulin binding transcription activator 2) The protein encoded by this gene is a member of the calmodulin-binding transcription activator protein family. Members of this family share a common domain structure that consists of a transcription activation domain, a DNA-binding domain, and a calmodulin-binding domain. The encoded protein may be a transcriptional coactivator of genes involved in cardiac growth. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Jan 2010]

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=0.02020657).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAMTA2	NM_015099.4	c.799G>A	p.Ala267Thr	missense_variant	9/23	ENST00000348066.8	NP_055914.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAMTA2	ENST00000348066.8	c.799G>A	p.Ala267Thr	missense_variant	9/23	1	NM_015099.4	ENSP00000321813	P4

Frequencies

GnomAD3 genomes Cov.: 19

GnomAD3 exomes AF: 0.00000805 AC: 2 AN: 248402 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 134884

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000581

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1457038 Hom.: 0 Cov.: 35 AF XY: 0.00000138 AC XY: 1 AN XY: 724898

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000448

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: 9.02e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 19

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	0.60
DANN	Benign	0.88
DEOGEN2	Benign	0.0026	.;.;T;.;T
Eigen	Benign	-2.2
Eigen_PC	Benign	-2.2
FATHMM_MKL	Benign	0.054	N
LIST_S2	Benign	0.071	T;T;T;T;T
M_CAP	Benign	0.0062	T
MetaRNN	Benign	0.020	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.34	.;.;.;.;N
MutationTaster	Benign	1.0	P;P;P;P;P;P
PrimateAI	Benign	0.34	T
PROVEAN	Benign	0.13	N;N;.;N;N
REVEL	Benign	0.036
Sift	Benign	0.19	T;T;.;T;T
Sift4G	Benign	0.27	T;T;T;T;T
Polyphen		0.0	.;B;.;B;B
Vest4		0.048
MutPred		0.10		.;.;.;.;Gain of glycosylation at A267 (P = 0.0046);
MVP		0.16
MPC		0.21
ClinPred		0.063	T
GERP RS		-2.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.028
gMVP		0.24

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: rs238234; hg19: chr17-4883818;