Variant 1-40069810-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM1BP4_ModerateBS2

The NM_006367.4(CAP1):c.929C>T(p.Ser310Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000936 in 1,602,994 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., 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: 5.77

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:

CAP1 (HGNC:):

CAP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM1

In a modified_residue Phosphoserine (size 0) in uniprot entity CAP1_HUMAN

BP4

Computational evidence support a benign effect (MetaRNN=0.15370604).

BS2

High AC in GnomAd4 at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAP1	NM_006367.4 linkuse as main transcript	c.929C>T	p.Ser310Phe	missense_variant	9/13	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.929C>T	p.Ser310Phe	missense_variant	9/13	1	NM_006367.4	ENSP00000361891.3		Q01518-1

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000423

AC:

AN:

236558

Hom.:

AF XY:

0.00

AC XY:

AN XY:

128256

show subpopulations

Gnomad AFR exome

AF:

0.0000654

Gnomad AMR exome

AF:

0.00

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000482

AC:

AN:

1450846

Hom.:

Cov.:

AF XY:

0.00000555

AC XY:

AN XY:

721282

show subpopulations

Gnomad4 AFR exome

AF:

0.0000909

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:

0.00000361

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000526

AC:

AN:

152148

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.000193

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000443

Hom.:

Bravo

AF:

0.0000453

ESP6500AA

AF:

0.000263

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00000828

AC:

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

Jul 05, 2023

The c.929C>T (p.S310F) alteration is located in exon 9 (coding exon 8) of the CAP1 gene. This alteration results from a C to T substitution at nucleotide position 929, causing the serine (S) at amino acid position 310 to be replaced by a phenylalanine (F). 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

0.11

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.24

T;.;T;.;.;T

Eigen

Benign

-0.11

Eigen_PC

Benign

0.045

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.60

.;.;.;.;T;T

M_CAP

Benign

0.0062

MetaRNN

Benign

0.15

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

L;.;L;.;.;L

MutationTaster

Benign

1.0

D;D;D;D;D;D

PrimateAI

Benign

0.40

PROVEAN

Uncertain

-2.8

D;D;D;D;D;D

REVEL

Benign

0.075

Sift

Benign

0.29

T;T;T;T;T;T

Sift4G

Benign

0.11

T;T;T;T;T;T

Polyphen

0.0030

B;.;B;.;.;B

Vest4

0.32

MVP

0.33

MPC

0.36

ClinPred

0.17

GERP RS

5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.19

gMVP

0.24

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