chr7-134867769-G-T

Variant names:

• chr7-134867769-G-T
• NM_033138.4:c.36G>T

Variant summary

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

The NM_033138.4(CALD1):​c.36G>T​(p.Arg12Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CALD1 NM_033138.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.27
• Publications: 0 publications found

Genes affected

CALD1 (HGNC:1441): (caldesmon 1) This gene encodes a calmodulin- and actin-binding protein that plays an essential role in the regulation of smooth muscle and nonmuscle contraction. The conserved domain of this protein possesses the binding activities to Ca(2+)-calmodulin, actin, tropomyosin, myosin, and phospholipids. This protein is a potent inhibitor of the actin-tropomyosin activated myosin MgATPase, and serves as a mediating factor for Ca(2+)-dependent inhibition of smooth muscle contraction. Alternative splicing of this gene results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2008]

ENSG00000286458 (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_033138.4. 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
	CALD1	NM_033138.4	MANE Select	c.36G>T	p.Arg12Ser	missense	Exon 3 of 15	NP_149129.2
	CALD1	NM_001438765.1		c.36G>T	p.Arg12Ser	missense	Exon 3 of 15	NP_001425694.1
	CALD1	NM_001438767.1		c.36G>T	p.Arg12Ser	missense	Exon 3 of 15	NP_001425696.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CALD1	ENST00000361675.7	TSL:1 MANE Select	c.36G>T	p.Arg12Ser	missense	Exon 3 of 15	ENSP00000354826.2	Q05682-1
	CALD1	ENST00000361901.6	TSL:1	c.36G>T	p.Arg12Ser	missense	Exon 3 of 14	ENSP00000354513.2	Q05682-4
	CALD1	ENST00000866426.1		c.36G>T	p.Arg12Ser	missense	Exon 4 of 16	ENSP00000536485.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 32

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	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.030
CADD	Benign	22
DANN	Benign	0.86
DEOGEN2	Benign	0.29	T
Eigen	Benign	0.043
Eigen_PC	Benign	0.025
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.030	D
MetaRNN	Uncertain	0.59	D
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.97	L
PhyloP100		1.3
PrimateAI	Pathogenic	0.90	D
PROVEAN	Uncertain	-2.4	N
REVEL	Uncertain	0.30
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.017	D
Polyphen		1.0	D
Vest4		0.76
MutPred		0.54		Gain of phosphorylation at R12 (P = 2e-04)
MVP		0.92
MPC		0.17
ClinPred		0.74	D
GERP RS		1.6
Varity_R		0.29
gMVP		0.10
Mutation Taster		=59/41	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

hg19: chr7-134552520;