Genetic Variant CALD1:p.Ser171Tyr (chr7-134933281-C-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_033138.4(CALD1):c.512C>A(p.Ser171Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000412 in 1,455,720 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S171F) has been classified as Benign.

Frequency

Genomes: not found (cov: 29)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

CALD1
NM_033138.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.71

Publications

6 publications found

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:

ENSG00000286458 (HGNC:):

ENSG00000286458 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAdExome4 at 6 AD gene.

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CALD1	NM_033138.4	MANE Select	c.512C>A	p.Ser171Tyr	missense	Exon 5 of 15	NP_149129.2
CALD1	NM_001438765.1		c.512C>A	p.Ser171Tyr	missense	Exon 5 of 15	NP_001425694.1
CALD1	NM_001438766.1		c.494C>A	p.Ser165Tyr	missense	Exon 3 of 13	NP_001425695.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CALD1	ENST00000361675.7	TSL:1 MANE Select	c.512C>A	p.Ser171Tyr	missense	Exon 5 of 15	ENSP00000354826.2	Q05682-1
CALD1	ENST00000393118.7	TSL:1	c.494C>A	p.Ser165Tyr	missense	Exon 3 of 13	ENSP00000376826.2	Q05682-3
CALD1	ENST00000361901.6	TSL:1	c.512C>A	p.Ser171Tyr	missense	Exon 5 of 14	ENSP00000354513.2	Q05682-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000412

AC:

AN:

1455720

Hom.:

Cov.:

AF XY:

0.00000415

AC XY:

AN XY:

723732

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33016

American (AMR)

AF:

0.00

AC:

AN:

44418

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26092

East Asian (EAS)

AF:

0.000128

AC:

AN:

39070

South Asian (SAS)

AF:

0.00

AC:

AN:

84970

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53142

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

9.02e-7

AC:

AN:

1109108

Other (OTH)

AF:

0.00

AC:

AN:

60138

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.016

BayesDel_noAF

Benign

-0.26

CADD

Uncertain

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.31

Eigen

Uncertain

0.62

Eigen_PC

Uncertain

0.60

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.97

M_CAP

Benign

0.016

MetaRNN

Uncertain

0.50

MetaSVM

Benign

-0.68

MutationAssessor

Uncertain

2.6

PhyloP100

3.7

PrimateAI

Benign

0.46

PROVEAN

Uncertain

-3.7

REVEL

Benign

0.20

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.014

Polyphen

0.95

Vest4

0.51

MutPred

0.44

Loss of phosphorylation at S171 (P = 0.0447)

MVP

0.42

MPC

0.19

ClinPred

0.99

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.40

gMVP

0.16

Mutation Taster

=74/26

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over