Genetic Variant ACTBL2:p.Val371Leu (chr5-57481597-C-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001017992.4(ACTBL2):c.1111G>C(p.Val371Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000093 in 1,612,408 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V371I) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

ACTBL2
NM_001017992.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.96

Publications

1 publications found

Variant links:

Genes affected

ACTBL2 (HGNC:17780): (actin beta like 2) Predicted to enable protein kinase binding activity. Predicted to be a structural constituent of postsynaptic actin cytoskeleton. Predicted to be involved in axonogenesis and cell motility. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

ACTBL2 links:

RMEL3 (HGNC:53975): (enriched in melanoma 3)

RMEL3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAd4 at 8 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001017992.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACTBL2	NM_001017992.4	MANE Select	c.1111G>C	p.Val371Leu	missense	Exon 1 of 1	NP_001017992.1	Q562R1
	RMEL3	NR_186596.1		n.73-12478C>G		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ACTBL2	ENST00000423391.3	TSL:6 MANE Select	c.1111G>C	p.Val371Leu	missense	Exon 1 of 1	ENSP00000416706.1	Q562R1
RMEL3	ENST00000506106.1	TSL:2	n.120-12478C>G		intron	N/A
RMEL3	ENST00000771489.1		n.274-7057C>G		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152092

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000280

AC:

AN:

250366

AF XY:

0.0000222

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.0000581

Gnomad ASJ exome

AF:

0.00

Gnomad EAS 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:

0.00000479

AC:

AN:

1460198

Hom.:

Cov.:

AF XY:

0.00000551

AC XY:

AN XY:

726342

show subpopulations

African (AFR)

AF:

0.000120

AC:

AN:

33436

American (AMR)

AF:

0.0000672

AC:

AN:

44618

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26052

East Asian (EAS)

AF:

0.00

AC:

AN:

39684

South Asian (SAS)

AF:

0.00

AC:

AN:

86098

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53404

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5132

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111502

Other (OTH)

AF:

0.00

AC:

AN:

60272

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000526

AC:

AN:

152210

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74402

show subpopulations

African (AFR)

AF:

0.000193

AC:

AN:

41544

American (AMR)

AF:

0.00

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5166

South Asian (SAS)

AF:

0.00

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10600

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68014

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000529

ExAC

AF:

0.0000494

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.84

BayesDel_addAF

Uncertain

0.16

BayesDel_noAF

Pathogenic

0.30

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.44

Eigen

Uncertain

0.40

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.97

M_CAP

Uncertain

0.086

MetaRNN

Uncertain

0.53

MetaSVM

Pathogenic

1.1

MutationAssessor

Uncertain

2.9

PhyloP100

5.0

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-1.2

REVEL

Pathogenic

0.77

Sift4G

Uncertain

0.040

Polyphen

0.35

Vest4

0.71

MVP

0.67

MPC

0.14

ClinPred

0.57

GERP RS

4.1

Varity_R

0.53

gMVP

0.14

Mutation Taster

=89/11

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over