rs368954349

Variant names:

• chr17-4969182-G-C
• rs368954349
• NM_015099.4:c.3438C>G

Your query was ambiguous. Multiple possible variants found:

• chr17-4969182-G-C
• chr17-4969182-G-A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_015099.4(CAMTA2):​c.3438C>G​(p.His1146Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000546 in 1,610,836 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000058 (0 hom.)
• Consequence: CAMTA2 NM_015099.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.34
• Publications: 0 publications found

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]

ENSG00000234203 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.15071318).
• BS2: High AC in GnomAdExome4 at 84 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015099.4. 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
	CAMTA2	NM_015099.4	MANE Select	c.3438C>G	p.His1146Gln	missense	Exon 21 of 23	NP_055914.2
	CAMTA2	NM_001171167.2		c.3507C>G	p.His1169Gln	missense	Exon 21 of 23	NP_001164638.1	O94983-6
	CAMTA2	NM_001171168.2		c.3435C>G	p.His1145Gln	missense	Exon 20 of 22	NP_001164639.1	O94983-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAMTA2	ENST00000348066.8	TSL:1 MANE Select	c.3438C>G	p.His1146Gln	missense	Exon 21 of 23	ENSP00000321813.7	O94983-1
	CAMTA2	ENST00000414043.7	TSL:1	c.3507C>G	p.His1169Gln	missense	Exon 21 of 23	ENSP00000412886.3	O94983-6
	CAMTA2	ENST00000361571.9	TSL:1	c.3435C>G	p.His1145Gln	missense	Exon 20 of 22	ENSP00000354828.5	O94983-4

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152250 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000406 AC: 1 AN: 246430 AF XY: 0.00000747

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000893

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000576 AC: 84 AN: 1458468 Hom.: 0 Cov.: 32 AF XY: 0.0000634 AC XY: 46 AN XY: 725644

African (AFR) AF: 0.00 AC: 0 AN: 33448

American (AMR) AF: 0.00 AC: 0 AN: 44530

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26052

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86136

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51082

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5746

European-Non Finnish (NFE) AF: 0.0000747 AC: 83 AN: 1111460

Other (OTH) AF: 0.0000166 AC: 1 AN: 60322

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152368 Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3 AN XY: 74512

African (AFR) AF: 0.0000240 AC: 1 AN: 41592

American (AMR) AF: 0.00 AC: 0 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10632

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68040

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000151

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000117 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0034	T
Eigen	Uncertain	0.21
Eigen_PC	Benign	0.19
FATHMM_MKL	Benign	0.76	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L
PhyloP100		1.3
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.060
Sift	Benign	0.077	T
Sift4G	Benign	0.37	T
Polyphen		0.96	D
Vest4		0.32
MutPred		0.22		Loss of catalytic residue at H1146 (P = 0.0253)
MVP		0.49
MPC		2.3
ClinPred		0.60	D
GERP RS		3.6
Varity_R		0.12
gMVP		0.61
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs368954349; hg19: chr17-4872477;