17-4970530-T-G

Variant names:

• chr17-4970530-T-G
• rs754591995
• NM_015099.4:c.2815A>C

Variant summary

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

The NM_015099.4(CAMTA2):​c.2815A>C​(p.Met939Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000686 in 1,457,196 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. M939V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CAMTA2 NM_015099.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.15
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.2815A>C	p.Met939Leu	missense	Exon 17 of 23	NP_055914.2
	CAMTA2	NM_001171167.2		c.2884A>C	p.Met962Leu	missense	Exon 17 of 23	NP_001164638.1	O94983-6
	CAMTA2	NM_001171168.2		c.2812A>C	p.Met938Leu	missense	Exon 16 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.2815A>C	p.Met939Leu	missense	Exon 17 of 23	ENSP00000321813.7	O94983-1
	CAMTA2	ENST00000414043.7	TSL:1	c.2884A>C	p.Met962Leu	missense	Exon 17 of 23	ENSP00000412886.3	O94983-6
	CAMTA2	ENST00000361571.9	TSL:1	c.2812A>C	p.Met938Leu	missense	Exon 16 of 22	ENSP00000354828.5	O94983-4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457196 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 724892

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39666

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49322

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

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111536

Other (OTH) AF: 0.00 AC: 0 AN: 60326

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.60
BayesDel_addAF	Uncertain	0.066	T
BayesDel_noAF	Benign	-0.14
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.038	T
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.013	T
MetaRNN	Uncertain	0.54	D
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	1.5	L
PhyloP100		5.2
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.18
Sift	Benign	0.039	D
Sift4G	Benign	0.12	T
Polyphen		0.80	P
Vest4		0.67
MutPred		0.33		Loss of methylation at K944 (P = 0.0701)
MVP		0.46
MPC		0.67
ClinPred		0.84	D
GERP RS		5.0
Varity_R		0.47
gMVP		0.52

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: rs754591995; hg19: chr17-4873825;