14-24065005-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_138360.4(CARMIL3):​c.3128C>T​(p.Pro1043Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,459,878 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

CARMIL3
NM_138360.4 missense

Scores

7
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.18
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 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CARMIL3NM_138360.4 linkc.3128C>T p.Pro1043Leu 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.3128C>T p.Pro1043Leu missense_variant Exon 33 of 40 5 NM_138360.4 ENSP00000340467.5 Q8ND23-1
CARMIL3ENST00000560349.1 linkn.1482C>T non_coding_transcript_exon_variant Exon 5 of 11 1
CARMIL3ENST00000559694.5 linkn.2658C>T non_coding_transcript_exon_variant Exon 18 of 24 5

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
0.00000411
AC:
6
AN:
1459878
Hom.:
0
Cov.:
32
AF XY:
0.00000413
AC XY:
3
AN XY:
726266
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:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000450
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.0000151

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Sep 01, 2021
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.3128C>T (p.P1043L) 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 3128, causing the proline (P) at amino acid position 1043 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
0.10
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.43
CADD
Benign
22
DANN
Uncertain
1.0
DEOGEN2
Benign
0.13
T
Eigen
Uncertain
0.34
Eigen_PC
Uncertain
0.27
FATHMM_MKL
Benign
0.61
D
M_CAP
Benign
0.061
D
MetaRNN
Uncertain
0.57
D
MetaSVM
Benign
-0.60
T
PrimateAI
Uncertain
0.66
T
PROVEAN
Uncertain
-4.1
D
REVEL
Benign
0.11
Sift
Uncertain
0.020
D
Sift4G
Benign
0.066
T
Polyphen
1.0
D
Vest4
0.57
MutPred
0.32
Gain of catalytic residue at P1043 (P = 0.0235);
MVP
0.43
MPC
0.35
ClinPred
0.95
D
GERP RS
4.8
Varity_R
0.16
gMVP
0.27

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.

Other links and lift over

dbSNP: rs1393152505; hg19: chr14-24534214; COSMIC: COSV57725332; COSMIC: COSV57725332; API