Variant chr1-40064365-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2

The NM_006367.4(CAP1):c.433G>T(p.Ala145Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,858 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

CAP1
NM_006367.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.19

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 made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.837

BS2

High AC in GnomAdExome4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAP1	NM_006367.4 linkuse as main transcript	c.433G>T	p.Ala145Ser	missense_variant	5/13	ENST00000372805.8	NP_006358.2	Q01518-1D3DPU2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAP1	ENST00000372805.8 linkuse as main transcript	c.433G>T	p.Ala145Ser	missense_variant	5/13	1	NM_006367.4	ENSP00000361891.3		Q01518-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1461858

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727242

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000630

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000312

Hom.:

Bravo

AF:

0.00000378

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

Dec 02, 2022

The c.433G>T (p.A145S) alteration is located in exon 5 (coding exon 4) of the CAP1 gene. This alteration results from a G to T substitution at nucleotide position 433, causing the alanine (A) at amino acid position 145 to be replaced by a serine (S). 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

0.19

BayesDel_addAF

Benign

-0.036

BayesDel_noAF

Benign

-0.29

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.069

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

Eigen

Pathogenic

0.79

Eigen_PC

Pathogenic

0.78

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.99

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

M_CAP

Benign

0.011

MetaRNN

Pathogenic

0.84

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

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.6

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

MutationTaster

Benign

1.0

D;D;D;D;D;D

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-1.6

N;N;N;N;N;N;N;N;N;N;N;N;N;N

REVEL

Benign

0.25

Sift

Benign

0.17

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

Sift4G

Benign

0.18

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

Polyphen

0.99

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

Vest4

0.66

MutPred

0.78

Gain of disorder (P = 0.1126);.;Gain of disorder (P = 0.1126);Gain of disorder (P = 0.1126);Gain of disorder (P = 0.1126);Gain of disorder (P = 0.1126);Gain of disorder (P = 0.1126);.;.;Gain of disorder (P = 0.1126);.;Gain of disorder (P = 0.1126);Gain of disorder (P = 0.1126);Gain of disorder (P = 0.1126);

MVP

0.46

MPC

0.82

ClinPred

0.93

GERP RS

5.4

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.7

Varity_R

0.59

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

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