NM_015215.4:c.39C>T

Variant names:

• chr1-6785569-C-T
• rs1174522704
• NM_015215.4:c.39C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_015215.4(CAMTA1):​c.39C>T​(p.Ser13Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000216 in 927,844 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 26)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: CAMTA1 NM_015215.4 synonymous
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.63
• Publications: 0 publications found

Genes affected

CAMTA1 (HGNC:18806): (calmodulin binding transcription activator 1) The protein encoded by this gene contains a CG1 DNA-binding domain, a transcription factor immunoglobulin domain, ankyrin repeats, and calmodulin-binding IQ motifs. The encoded protein is thought to be a transcription factor and may be a tumor suppressor. However, a translocation event is sometimes observed between this gene and the WWTR1 gene, with the resulting WWTR1-CAMTA1 oncoprotein leading to epithelioid hemangioendothelioma, a malignant vascular cancer. [provided by RefSeq, Mar 2017]

CAMTA1 Gene-Disease associations (from GenCC):

• cerebellar dysfunction with variable cognitive and behavioral abnormalities

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP7: Synonymous conserved (PhyloP=1.63 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015215.4. 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
	CAMTA1	NM_015215.4	MANE Select	c.39C>T	p.Ser13Ser	synonymous	Exon 1 of 23	NP_056030.1	Q9Y6Y1-1
	CAMTA1	NM_001349608.2		c.19C>T	p.Pro7Ser	missense	Exon 1 of 22	NP_001336537.1
	CAMTA1	NM_001349612.2		c.19C>T	p.Pro7Ser	missense	Exon 1 of 23	NP_001336541.1	A0A8V8TQ65

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAMTA1	ENST00000303635.12	TSL:1 MANE Select	c.39C>T	p.Ser13Ser	synonymous	Exon 1 of 23	ENSP00000306522.6	Q9Y6Y1-1
	CAMTA1	ENST00000476864.2	TSL:1	c.39C>T	p.Ser13Ser	synonymous	Exon 1 of 22	ENSP00000452319.2	A0A0C4DGL0
	CAMTA1	ENST00000473578.5	TSL:1	c.39C>T	p.Ser13Ser	synonymous	Exon 1 of 4	ENSP00000451388.1	Q9Y6Y1-3

Frequencies

GnomAD3 genomes Cov.: 26

GnomAD4 exome AF: 0.00000216 AC: 2 AN: 927844 Hom.: 0 Cov.: 31 AF XY: 0.00000226 AC XY: 1 AN XY: 441988

African (AFR) AF: 0.00 AC: 0 AN: 17492

American (AMR) AF: 0.00 AC: 0 AN: 9282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9840

East Asian (EAS) AF: 0.00 AC: 0 AN: 5234

South Asian (SAS) AF: 0.0000668 AC: 2 AN: 29934

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 18824

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2272

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 804016

Other (OTH) AF: 0.00 AC: 0 AN: 30950

GnomAD4 genome Cov.: 26

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	17
DANN	Benign	0.97
PhyloP100		1.6
PromoterAI		-0.18	Neutral
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.1
Mutation Taster		=98/2	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: rs1174522704; hg19: chr1-6845629;