dbSNP rs10146906: CARMIL3:p.Leu1022Met (chr14-24064330-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_138360.4(CARMIL3):c.3064C>A(p.Leu1022Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.437 in 1,607,792 control chromosomes in the GnomAD database, including 158,465 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.44 ( 15415 hom., cov: 31)

Exomes 𝑓: 0.44 ( 143050 hom. )

Consequence

CARMIL3
NM_138360.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.21

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]

CARMIL3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.001649648).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.476 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CARMIL3	NM_138360.4 link	c.3064C>A	p.Leu1022Met	missense_variant	Exon 32 of 40	ENST00000342740.6	NP_612369.3	Q8ND23-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CARMIL3	ENST00000342740.6 link	c.3064C>A	p.Leu1022Met	missense_variant	Exon 32 of 40	5	NM_138360.4	ENSP00000340467.5	Q8ND23-1
CARMIL3	ENST00000560349.1 link	n.1418C>A		non_coding_transcript_exon_variant	Exon 4 of 11	1
CARMIL3	ENST00000559694.5 link	n.2594C>A		non_coding_transcript_exon_variant	Exon 17 of 24	5

Frequencies

GnomAD3 genomes

AF:

0.442

AC:

67085

AN:

151820

Hom.:

15406

Cov.:

show subpopulations

Gnomad AFR

AF:

0.481

Gnomad AMI

AF:

0.324

Gnomad AMR

AF:

0.440

Gnomad ASJ

AF:

0.364

Gnomad EAS

AF:

0.0458

Gnomad SAS

AF:

0.290

Gnomad FIN

AF:

0.438

Gnomad MID

AF:

0.376

Gnomad NFE

AF:

0.466

Gnomad OTH

AF:

0.431

GnomAD3 exomes

AF:

0.404

AC:

98377

AN:

243214

Hom.:

21289

AF XY:

0.400

AC XY:

52560

AN XY:

131422

show subpopulations

Gnomad AFR exome

AF:

0.481

Gnomad AMR exome

AF:

0.463

Gnomad ASJ exome

AF:

0.371

Gnomad EAS exome

AF:

0.0457

Gnomad SAS exome

AF:

0.296

Gnomad FIN exome

AF:

0.442

Gnomad NFE exome

AF:

0.460

Gnomad OTH exome

AF:

0.411

GnomAD4 exome

AF:

0.436

AC:

634721

AN:

1455854

Hom.:

143050

Cov.:

AF XY:

0.432

AC XY:

312847

AN XY:

723812

show subpopulations

Gnomad4 AFR exome

AF:

0.484

Gnomad4 AMR exome

AF:

0.462

Gnomad4 ASJ exome

AF:

0.366

Gnomad4 EAS exome

AF:

0.0375

Gnomad4 SAS exome

AF:

0.302

Gnomad4 FIN exome

AF:

0.443

Gnomad4 NFE exome

AF:

0.461

Gnomad4 OTH exome

AF:

0.413

GnomAD4 genome

AF:

0.442

AC:

67136

AN:

151938

Hom.:

15415

Cov.:

AF XY:

0.435

AC XY:

32291

AN XY:

74276

show subpopulations

Gnomad4 AFR

AF:

0.481

Gnomad4 AMR

AF:

0.441

Gnomad4 ASJ

AF:

0.364

Gnomad4 EAS

AF:

0.0453

Gnomad4 SAS

AF:

0.291

Gnomad4 FIN

AF:

0.438

Gnomad4 NFE

AF:

0.466

Gnomad4 OTH

AF:

0.427

Alfa

AF:

0.438

Hom.:

36247

Bravo

AF:

0.444

TwinsUK

AF:

0.459

AC:

1703

ALSPAC

AF:

0.425

AC:

1638

ESP6500AA

AF:

0.487

AC:

2144

ESP6500EA

AF:

0.453

AC:

3899

ExAC

AF:

0.400

AC:

48532

Asia WGS

AF:

0.179

AC:

625

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.66

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.015

Eigen

Benign

-0.59

Eigen_PC

Benign

-0.35

FATHMM_MKL

Benign

0.053

MetaRNN

Benign

0.0016

MetaSVM

Benign

-0.92

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-0.26

REVEL

Benign

0.12

Sift

Benign

1.0

Sift4G

Benign

0.22

Polyphen

0.0

Vest4

0.066

MPC

0.33

ClinPred

0.013

GERP RS

5.3

Varity_R

0.055

gMVP

0.26

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over