14-24064330-C-A

Variant names:

• chr14-24064330-C-A
• rs10146906
• NM_138360.4:c.3064C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.44 (15415 hom., cov: 31)
  • Exomes 𝑓: 0.44 (143050 hom.)
• Consequence: CARMIL3 NM_138360.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.21
• Publications: 26 publications found

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]

DHRS4-AS1 (HGNC:23175): (DHRS4 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138360.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CARMIL3	NM_138360.4	MANE Select	c.3064C>A	p.Leu1022Met	missense	Exon 32 of 40	NP_612369.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CARMIL3	ENST00000342740.6	TSL:5 MANE Select	c.3064C>A	p.Leu1022Met	missense	Exon 32 of 40	ENSP00000340467.5
	CARMIL3	ENST00000560349.1	TSL:1	n.1418C>A		non_coding_transcript_exon	Exon 4 of 11
	CARMIL3	ENST00000559694.5	TSL:5	n.2594C>A		non_coding_transcript_exon	Exon 17 of 24

Frequencies

GnomAD3 genomes AF: 0.442 AC: 67085 AN: 151820 Hom.: 15406 Cov.: 31

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

GnomAD2 exomes AF: 0.404 AC: 98377 AN: 243214 AF XY: 0.400

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 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.: 34 AF XY: 0.432 AC XY: 312847 AN XY: 723812

African (AFR) AF: 0.484 AC: 16170 AN: 33390

American (AMR) AF: 0.462 AC: 20432 AN: 44270

Ashkenazi Jewish (ASJ) AF: 0.366 AC: 9517 AN: 26012

East Asian (EAS) AF: 0.0375 AC: 1487 AN: 39624

South Asian (SAS) AF: 0.302 AC: 25800 AN: 85386

European-Finnish (FIN) AF: 0.443 AC: 23464 AN: 53008

Middle Eastern (MID) AF: 0.399 AC: 2291 AN: 5738

European-Non Finnish (NFE) AF: 0.461 AC: 510710 AN: 1108318

Other (OTH) AF: 0.413 AC: 24850 AN: 60108

GnomAD4 genome AF: 0.442 AC: 67136 AN: 151938 Hom.: 15415 Cov.: 31 AF XY: 0.435 AC XY: 32291 AN XY: 74276

African (AFR) AF: 0.481 AC: 19937 AN: 41438

American (AMR) AF: 0.441 AC: 6732 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.364 AC: 1262 AN: 3470

East Asian (EAS) AF: 0.0453 AC: 234 AN: 5166

South Asian (SAS) AF: 0.291 AC: 1402 AN: 4814

European-Finnish (FIN) AF: 0.438 AC: 4627 AN: 10560

Middle Eastern (MID) AF: 0.370 AC: 108 AN: 292

European-Non Finnish (NFE) AF: 0.466 AC: 31640 AN: 67912

Other (OTH) AF: 0.427 AC: 900 AN: 2106

Alfa AF: 0.441 Hom.: 51495

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 v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	21
DANN	Benign	0.94
DEOGEN2	Benign	0.015	T
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.35
FATHMM_MKL	Benign	0.053	N
MetaRNN	Benign	0.0016	T
MetaSVM	Benign	-0.92	T
PhyloP100		3.2
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-0.26	N
REVEL	Benign	0.12
Sift	Benign	1.0	T
Sift4G	Benign	0.22	T
Polyphen		0.0	B
Vest4		0.066
MPC		0.33
ClinPred		0.013	T
GERP RS		5.3
Varity_R		0.055
gMVP		0.26
Mutation Taster		=97/3	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10146906; hg19: chr14-24533539; COSMIC: COSV57726458; COSMIC: COSV57726458;