7-134867753-G-T

Variant summary

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

The NM_033138.4(CALD1):​c.20G>T​(p.Arg7Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,078 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

CALD1
NM_033138.4 missense

Scores

7
8
4

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.25
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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
CALD1NM_033138.4 linkc.20G>T p.Arg7Leu missense_variant Exon 3 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.20G>T p.Arg7Leu missense_variant Exon 3 of 15 1 NM_033138.4 ENSP00000354826.2 Q05682-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000403
AC:
1
AN:
247860
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
133880
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000334
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.86e-7
AC:
1
AN:
1457078
Hom.:
0
Cov.:
27
AF XY:
0.00
AC XY:
0
AN XY:
724844
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000117
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.98
BayesDel_addAF
Pathogenic
0.20
D
BayesDel_noAF
Uncertain
0.050
CADD
Pathogenic
28
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.46
.;T;.;T;D;.;.;T
Eigen
Pathogenic
0.68
Eigen_PC
Pathogenic
0.71
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.93
.;D;D;.;D;D;D;D
M_CAP
Benign
0.037
D
MetaRNN
Uncertain
0.71
D;D;D;D;D;D;D;D
MetaSVM
Benign
-0.47
T
MutationAssessor
Benign
0.97
L;.;L;.;L;L;.;.
PrimateAI
Pathogenic
0.93
D
PROVEAN
Uncertain
-2.7
D;D;D;D;D;D;D;D
REVEL
Uncertain
0.43
Sift
Pathogenic
0.0
D;D;D;D;D;D;D;D
Sift4G
Uncertain
0.0070
D;D;D;D;D;D;D;D
Polyphen
1.0
D;.;.;.;D;D;.;.
Vest4
0.86
MutPred
0.59
Gain of helix (P = 0.2294);Gain of helix (P = 0.2294);Gain of helix (P = 0.2294);Gain of helix (P = 0.2294);Gain of helix (P = 0.2294);Gain of helix (P = 0.2294);Gain of helix (P = 0.2294);Gain of helix (P = 0.2294);
MVP
0.72
MPC
0.18
ClinPred
0.86
D
GERP RS
5.5
Varity_R
0.41
gMVP
0.13

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: rs142583902; hg19: chr7-134552504; API