1-40069845-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006367.4(CAP1):​c.964C>T​(p.Leu322Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000314 in 1,590,162 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 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CAP1
NM_006367.4 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.25
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.23516425).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CAP1NM_006367.4 linkc.964C>T p.Leu322Phe missense_variant 9/13 ENST00000372805.8 NP_006358.2 Q01518-1D3DPU2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CAP1ENST00000372805.8 linkc.964C>T p.Leu322Phe missense_variant 9/131 NM_006367.4 ENSP00000361891.3 Q01518-1

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152194
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000445
AC:
1
AN:
224612
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
122058
show subpopulations
Gnomad AFR exome
AF:
0.00
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:
0.000190
GnomAD4 exome
AF:
0.00000139
AC:
2
AN:
1437968
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
714276
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000256
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:
0.00
Gnomad4 OTH exome
AF:
0.0000169
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152194
Hom.:
0
Cov.:
32
AF XY:
0.0000404
AC XY:
3
AN XY:
74340
show subpopulations
Gnomad4 AFR
AF:
0.0000241
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:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000604

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 submitterclinical testingAmbry GeneticsDec 26, 2023The c.964C>T (p.L322F) 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 964, causing the leucine (L) at amino acid position 322 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
0.10
BayesDel_addAF
Benign
-0.21
T
BayesDel_noAF
Benign
-0.53
CADD
Benign
19
DANN
Uncertain
0.98
DEOGEN2
Benign
0.018
T;.;T;.;.;T
Eigen
Benign
0.020
Eigen_PC
Benign
0.17
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Benign
0.75
.;.;.;.;T;T
M_CAP
Benign
0.012
T
MetaRNN
Benign
0.24
T;T;T;T;T;T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
0.79
N;.;N;.;.;N
PrimateAI
Uncertain
0.64
T
PROVEAN
Benign
0.61
N;N;N;N;N;N
REVEL
Benign
0.089
Sift
Benign
0.53
T;T;T;T;T;T
Sift4G
Benign
0.65
T;T;T;T;T;T
Polyphen
0.60
P;.;P;.;.;P
Vest4
0.44
MutPred
0.53
Gain of methylation at K317 (P = 0.0999);.;Gain of methylation at K317 (P = 0.0999);.;.;Gain of methylation at K317 (P = 0.0999);
MVP
0.31
MPC
0.80
ClinPred
0.25
T
GERP RS
4.7
Varity_R
0.33
gMVP
0.41

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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.

Other links and lift over

dbSNP: rs1159650749; hg19: chr1-40535517; API