Genetic Variant ACSM4:p.Phe141Ile (chr12-7310547-T-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001080454.2(ACSM4):c.421T>A(p.Phe141Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000125 in 1,605,156 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

ACSM4
NM_001080454.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.766

Publications

0 publications found

Variant links:

Genes affected

ACSM4 (HGNC:32016): (acyl-CoA synthetase medium chain family member 4) Predicted to enable decanoate-CoA ligase activity and fatty-acyl-CoA synthase activity. Predicted to be involved in acyl-CoA metabolic process and fatty acid biosynthetic process. Predicted to be active in mitochondrial matrix. [provided by Alliance of Genome Resources, Apr 2022]

ACSM4 links:

ENSG00000299889 (HGNC:):

ENSG00000299889 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1572966).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080454.2. 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
	ACSM4	NM_001080454.2	MANE Select	c.421T>A	p.Phe141Ile	missense	Exon 3 of 13	NP_001073923.1	P0C7M7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ACSM4	ENST00000399422.5	TSL:5 MANE Select	c.421T>A	p.Phe141Ile	missense	Exon 3 of 13	ENSP00000382349.4	P0C7M7
ENSG00000299889	ENST00000767257.1		n.167+6414A>T		intron	N/A
ACSM4	ENST00000533292.1	TSL:3	n.-126T>A		upstream_gene	N/A

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

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:

0.0000169

AC:

AN:

237144

AF XY:

0.0000156

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000231

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.88e-7

AC:

AN:

1452968

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

721966

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33296

American (AMR)

AF:

0.00

AC:

AN:

43888

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25904

East Asian (EAS)

AF:

0.0000254

AC:

AN:

39374

South Asian (SAS)

AF:

0.00

AC:

AN:

84478

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52296

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4710

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1108986

Other (OTH)

AF:

0.00

AC:

AN:

60036

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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:

0.00000657

AC:

AN:

152188

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41446

American (AMR)

AF:

0.00

AC:

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68030

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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:

0.0000189

ExAC

AF:

0.00000827

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.013

Eigen

Benign

-0.47

Eigen_PC

Benign

-0.36

FATHMM_MKL

Benign

0.53

LIST_S2

Benign

0.64

M_CAP

Benign

0.0051

MetaRNN

Benign

0.16

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.20

PhyloP100

0.77

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-0.78

REVEL

Benign

0.14

Sift

Benign

0.19

Sift4G

Benign

0.28

Polyphen

0.13

Vest4

0.46

MutPred

0.55

Gain of catalytic residue at R136 (P = 0)

MVP

0.15

MPC

0.12

ClinPred

0.12

GERP RS

3.5

Varity_R

0.30

gMVP

0.68

Mutation Taster

=88/12

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