7-134933065-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_033138.4(CALD1):ā€‹c.296G>Cā€‹(p.Arg99Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,613,886 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: š‘“ 0.000013 ( 0 hom., cov: 31)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

CALD1
NM_033138.4 missense

Scores

10
5
4

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 8.68
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.843

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CALD1NM_033138.4 linkc.296G>C p.Arg99Pro missense_variant Exon 5 of 15 ENST00000361675.7 NP_149129.2 Q05682-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CALD1ENST00000361675.7 linkc.296G>C p.Arg99Pro missense_variant Exon 5 of 15 1 NM_033138.4 ENSP00000354826.2 Q05682-1

Frequencies

GnomAD3 genomes
AF:
0.0000132
AC:
2
AN:
152022
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000483
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461864
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
727230
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000132
AC:
2
AN:
152022
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
74256
show subpopulations
Gnomad4 AFR
AF:
0.0000483
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.99
BayesDel_addAF
Pathogenic
0.33
D
BayesDel_noAF
Pathogenic
0.23
CADD
Pathogenic
29
DANN
Uncertain
0.99
DEOGEN2
Benign
0.36
.;T;.;T;.;.;.;.;T
Eigen
Pathogenic
0.86
Eigen_PC
Pathogenic
0.83
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Pathogenic
0.98
.;D;D;D;D;D;D;D;D
M_CAP
Benign
0.060
D
MetaRNN
Pathogenic
0.84
D;D;D;D;D;D;D;D;D
MetaSVM
Benign
-0.36
T
MutationAssessor
Uncertain
2.8
M;.;M;M;M;.;.;.;.
PrimateAI
Uncertain
0.65
T
PROVEAN
Pathogenic
-4.6
D;D;D;D;D;D;D;D;D
REVEL
Pathogenic
0.67
Sift
Pathogenic
0.0
D;D;D;D;D;D;D;D;D
Sift4G
Uncertain
0.012
D;D;D;D;D;D;D;D;D
Polyphen
1.0
D;.;.;D;D;.;D;D;.
Vest4
0.86
MutPred
0.61
Loss of MoRF binding (P = 0.0067);Loss of MoRF binding (P = 0.0067);Loss of MoRF binding (P = 0.0067);Loss of MoRF binding (P = 0.0067);Loss of MoRF binding (P = 0.0067);.;.;.;.;
MVP
0.89
MPC
0.21
ClinPred
1.0
D
GERP RS
5.4
Varity_R
0.88
gMVP
0.33

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs143639360; hg19: chr7-134617816; API