Variant 7-134933128-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_033138.4(CALD1):c.359A>C(p.Glu120Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000273 in 1,613,904 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

CALD1
NM_033138.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.36

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]

CALD1 links:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAd4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CALD1	NM_033138.4 linkuse as main transcript	c.359A>C	p.Glu120Ala	missense_variant	5/15	ENST00000361675.7	NP_149129.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CALD1	ENST00000361675.7 linkuse as main transcript	c.359A>C	p.Glu120Ala	missense_variant	5/15	1	NM_033138.4	ENSP00000354826		Q05682-1
	ENST00000665703.1 linkuse as main transcript	n.71+64955T>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152032

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000319

AC:

AN:

250928

Hom.:

AF XY:

0.0000295

AC XY:

AN XY:

135702

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000174

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000882

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000267

AC:

AN:

1461872

Hom.:

Cov.:

AF XY:

0.0000275

AC XY:

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000134

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:

0.0000288

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152032

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74250

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000416

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 02, 2021

The c.359A>C (p.E120A) alteration is located in exon 5 (coding exon 3) of the CALD1 gene. This alteration results from a A to C substitution at nucleotide position 359, causing the glutamic acid (E) at amino acid position 120 to be replaced by an alanine (A). 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

Benign

0.25

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.12

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.34

.;T;.;T;.;.;.;T

Eigen

Uncertain

0.42

Eigen_PC

Uncertain

0.49

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.96

.;D;D;D;D;D;D;D

M_CAP

Benign

0.029

MetaRNN

Uncertain

0.56

D;D;D;D;D;D;D;D

MetaSVM

Benign

-0.52

MutationAssessor

Uncertain

2.8

M;.;M;M;M;.;.;.

MutationTaster

Benign

0.84

D;D;D;D;D;D;D;D;D

PrimateAI

Uncertain

0.58

PROVEAN

Uncertain

-3.5

D;D;D;D;D;D;D;D

REVEL

Benign

0.26

Sift

Pathogenic

0.0

D;D;D;D;D;D;D;D

Sift4G

Uncertain

0.010

D;D;T;D;D;T;D;T

Polyphen

0.59

P;.;.;P;P;B;B;.

Vest4

0.47

MutPred

0.47

Gain of MoRF binding (P = 0.052);Gain of MoRF binding (P = 0.052);Gain of MoRF binding (P = 0.052);Gain of MoRF binding (P = 0.052);Gain of MoRF binding (P = 0.052);.;.;.;

MVP

0.57

MPC

0.16

ClinPred

0.88

GERP RS

5.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.28

gMVP

0.086

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over