7-134928792-C-A

Variant names:

• chr7-134928792-C-A
• NM_033138.4:c.110C>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_033138.4(CALD1):​c.110C>A​(p.Ala37Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: CALD1 NM_033138.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.79

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CALD1	NM_033138.4	c.110C>A	p.Ala37Glu	missense_variant	Exon 4 of 15	ENST00000361675.7	NP_149129.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CALD1	ENST00000361675.7	c.110C>A	p.Ala37Glu	missense_variant	Exon 4 of 15	1	NM_033138.4	ENSP00000354826.2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 30

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 04, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.110C>A (p.A37E) alteration is located in exon 4 (coding exon 2) of the CALD1 gene. This alteration results from a C to A substitution at nucleotide position 110, causing the alanine (A) at amino acid position 37 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.89
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.26	.;T;.;T;T;.;.;T;.;.;T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.91	.;D;D;.;D;D;D;D;D;D;D
M_CAP	Benign	0.035	D
MetaRNN	Uncertain	0.64	D;D;D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.54	T
MutationAssessor	Uncertain	2.4	M;.;M;.;M;M;.;.;.;.;.
PrimateAI	Pathogenic	0.84	D
PROVEAN	Uncertain	-2.9	D;D;D;D;D;D;D;D;D;D;D
REVEL	Uncertain	0.44
Sift	Benign	0.071	T;T;T;D;D;T;T;D;D;D;D
Sift4G	Benign	0.11	T;T;T;D;D;T;D;D;T;T;T
Polyphen		1.0	D;.;.;.;D;D;.;.;D;D;.
Vest4		0.53
MutPred		0.55		Loss of MoRF binding (P = 0.0343);Loss of MoRF binding (P = 0.0343);Loss of MoRF binding (P = 0.0343);Loss of MoRF binding (P = 0.0343);Loss of MoRF binding (P = 0.0343);Loss of MoRF binding (P = 0.0343);.;Loss of MoRF binding (P = 0.0343);.;.;.;
MVP		0.64
MPC		0.17
ClinPred		0.95	D
GERP RS		5.5
Varity_R		0.73
gMVP		0.40

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-134613543;