Genetic Variant CARMIL3:p.Leu1022Leu (chr14-24064330-C-T) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP7

The NM_138360.4(CARMIL3):c.3064C>T(p.Leu1022Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,368 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

CARMIL3
NM_138360.4 synonymous

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.28).

BP7

Synonymous conserved (PhyloP=3.21 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CARMIL3	NM_138360.4 link	c.3064C>T	p.Leu1022Leu	synonymous_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>T	p.Leu1022Leu	synonymous_variant	Exon 32 of 40	5	NM_138360.4	ENSP00000340467.5	Q8ND23-1
CARMIL3	ENST00000560349.1 link	n.1418C>T		non_coding_transcript_exon_variant	Exon 4 of 11	1
CARMIL3	ENST00000559694.5 link	n.2594C>T		non_coding_transcript_exon_variant	Exon 17 of 24	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000164

AC:

AN:

243214

Hom.:

AF XY:

0.0000228

AC XY:

AN XY:

131422

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000219

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:

6.86e-7

AC:

AN:

1457368

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

724512

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:

0.0000117

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.28

CADD

Benign

9.3

DANN

Benign

0.78

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