chr14-24065131-C-T

Variant summary

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

The NM_138360.4(CARMIL3):​c.3254C>T​(p.Pro1085Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000158 in 1,459,962 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000086 ( 0 hom., cov: 27)
Exomes 𝑓: 0.00017 ( 0 hom. )

Consequence

CARMIL3
NM_138360.4 missense

Scores

4
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.52
Variant links:
Genes affected
CARMIL3 (HGNC:20272): (capping protein regulator and myosin 1 linker 3) Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

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=0.16698736).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CARMIL3NM_138360.4 linkc.3254C>T p.Pro1085Leu missense_variant Exon 33 of 40 ENST00000342740.6 NP_612369.3 Q8ND23-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CARMIL3ENST00000342740.6 linkc.3254C>T p.Pro1085Leu missense_variant Exon 33 of 40 5 NM_138360.4 ENSP00000340467.5 Q8ND23-1
CARMIL3ENST00000560349.1 linkn.1608C>T non_coding_transcript_exon_variant Exon 5 of 11 1
CARMIL3ENST00000559694.5 linkn.2784C>T non_coding_transcript_exon_variant Exon 18 of 24 5

Frequencies

GnomAD3 genomes
AF:
0.0000864
AC:
13
AN:
150384
Hom.:
0
Cov.:
27
show subpopulations
Gnomad AFR
AF:
0.0000981
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:
0.000134
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000137
AC:
1
AN:
73092
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
38372
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:
0.0000401
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000166
AC:
218
AN:
1309578
Hom.:
0
Cov.:
34
AF XY:
0.000130
AC XY:
83
AN XY:
638914
show subpopulations
Gnomad4 AFR exome
AF:
0.0000712
Gnomad4 AMR exome
AF:
0.0000904
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:
0.000202
Gnomad4 OTH exome
AF:
0.0000742
GnomAD4 genome
AF:
0.0000864
AC:
13
AN:
150384
Hom.:
0
Cov.:
27
AF XY:
0.0000681
AC XY:
5
AN XY:
73454
show subpopulations
Gnomad4 AFR
AF:
0.0000981
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:
0.000134
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000245
Hom.:
0
ExAC
AF:
0.0000206
AC:
2

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Aug 02, 2021
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.3254C>T (p.P1085L) alteration is located in exon 33 (coding exon 33) of the CARMIL3 gene. This alteration results from a C to T substitution at nucleotide position 3254, causing the proline (P) at amino acid position 1085 to be replaced by a leucine (L). 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
0.089
BayesDel_addAF
Benign
-0.26
T
BayesDel_noAF
Benign
-0.48
CADD
Uncertain
24
DANN
Benign
0.96
DEOGEN2
Benign
0.021
T
Eigen
Benign
-0.59
Eigen_PC
Benign
-0.52
FATHMM_MKL
Uncertain
0.88
D
M_CAP
Uncertain
0.11
D
MetaRNN
Benign
0.17
T
MetaSVM
Benign
-1.1
T
PrimateAI
Uncertain
0.75
T
PROVEAN
Benign
-1.3
N
REVEL
Benign
0.098
Sift
Uncertain
0.0050
D
Sift4G
Benign
0.12
T
Polyphen
0.028
B
Vest4
0.39
MVP
0.15
MPC
0.32
ClinPred
0.17
T
GERP RS
2.0
Varity_R
0.070
gMVP
0.41

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs765445371; hg19: chr14-24534340; API