Genetic Variant NM_006367.4:c.722C>G (chr1-40067631-C-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_006367.4(CAP1):c.722C>G(p.Pro241Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000703 in 1,421,588 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. P241L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

CAP1
NM_006367.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.52

Publications

0 publications found

Variant links:

Genes affected

CAP1 (HGNC:20040): (cyclase associated actin cytoskeleton regulatory protein 1) The protein encoded by this gene is related to the S. cerevisiae CAP protein, which is involved in the cyclic AMP pathway. The human protein is able to interact with other molecules of the same protein, as well as with CAP2 and actin. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Aug 2016]

CAP1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006367.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CAP1	NM_006367.4	MANE Select	c.722C>G	p.Pro241Arg	missense	Exon 8 of 13	NP_006358.2	Q01518-1
CAP1	NM_001105530.2		c.722C>G	p.Pro241Arg	missense	Exon 8 of 13	NP_001099000.2	Q01518-1
CAP1	NM_001350475.2		c.722C>G	p.Pro241Arg	missense	Exon 9 of 14	NP_001337404.2	Q01518-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CAP1	ENST00000372805.8	TSL:1 MANE Select	c.722C>G	p.Pro241Arg	missense	Exon 8 of 13	ENSP00000361891.3	Q01518-1
CAP1	ENST00000372792.7	TSL:1	c.722C>G	p.Pro241Arg	missense	Exon 8 of 13	ENSP00000361878.2	Q01518-1
CAP1	ENST00000372797.7	TSL:1	c.722C>G	p.Pro241Arg	missense	Exon 8 of 13	ENSP00000361883.3	Q01518-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.03e-7

AC:

AN:

1421588

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

709342

show subpopulations

African (AFR)

AF:

0.0000315

AC:

AN:

31724

American (AMR)

AF:

0.00

AC:

AN:

40286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25278

East Asian (EAS)

AF:

0.00

AC:

AN:

38534

South Asian (SAS)

AF:

0.00

AC:

AN:

84660

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53212

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5642

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1083406

Other (OTH)

AF:

0.00

AC:

AN:

58846

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Uncertain

-0.040

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.23

Eigen

Uncertain

0.57

Eigen_PC

Uncertain

0.46

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.84

M_CAP

Uncertain

0.12

MetaRNN

Uncertain

0.67

MetaSVM

Uncertain

0.77

MutationAssessor

Pathogenic

3.5

PhyloP100

4.5

PrimateAI

Uncertain

0.62

PROVEAN

Pathogenic

-5.5

REVEL

Benign

0.17

Sift

Benign

0.077

Sift4G

Uncertain

0.033

Polyphen

0.99

Vest4

0.40

MutPred

0.41

Loss of glycosylation at P241 (P = 0.0067)

MVP

0.79

MPC

0.96

ClinPred

0.88

GERP RS

4.9

Varity_R

0.30

gMVP

0.48

Mutation Taster

=45/55

disease causing

(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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over