Genetic Variant ACSM1:p.Asn449Ser (chr16-20627270-T-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001318890.3(ACSM1):c.1346A>G(p.Asn449Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000667 in 1,587,462 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00040 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00070 ( 0 hom. )

Consequence

ACSM1
NM_001318890.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.99

Publications

3 publications found

Variant links:

Genes affected

ACSM1 (HGNC:18049): (acyl-CoA synthetase medium chain family member 1) Enables CoA-ligase activity. Predicted to be involved in acyl-CoA metabolic process and fatty acid biosynthetic process. Located in mitochondrial matrix. [provided by Alliance of Genome Resources, Apr 2022]

ACSM1 links:

ACSM3 (HGNC:10522): (acyl-CoA synthetase medium chain family member 3) Enables butyrate-CoA ligase activity. Predicted to be involved in acyl-CoA metabolic process and fatty acid biosynthetic process. Located in mitochondrion. Implicated in IgA glomerulonephritis. Biomarker of ulcerative colitis. [provided by Alliance of Genome Resources, Apr 2022]

ACSM3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.22359857).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001318890.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ACSM1	NM_001318890.3	MANE Select	c.1346A>G	p.Asn449Ser	missense	Exon 11 of 14	NP_001305819.1	Q08AH1-1
ACSM1	NM_052956.3		c.1346A>G	p.Asn449Ser	missense	Exon 10 of 13	NP_443188.2	Q08AH1-1
ACSM1	NR_134918.2		n.1249A>G		non_coding_transcript_exon	Exon 9 of 11

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ACSM1	ENST00000520010.6	TSL:1 MANE Select	c.1346A>G	p.Asn449Ser	missense	Exon 11 of 14	ENSP00000428047.1	Q08AH1-1
ACSM1	ENST00000307493.8	TSL:1	c.1346A>G	p.Asn449Ser	missense	Exon 10 of 13	ENSP00000301956.3	Q08AH1-1
ACSM1	ENST00000519745.5	TSL:1	n.*566A>G		non_coding_transcript_exon	Exon 9 of 11	ENSP00000428650.1	Q08AH1-2

Frequencies

GnomAD3 genomes

AF:

0.000401

AC:

AN:

152108

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000765

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000379

AC:

AN:

232364

AF XY:

0.000389

show subpopulations

Gnomad AFR exome

AF:

0.000206

Gnomad AMR exome

AF:

0.0000985

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000709

Gnomad OTH exome

AF:

0.000364

GnomAD4 exome

AF:

0.000695

AC:

998

AN:

1435354

Hom.:

Cov.:

AF XY:

0.000677

AC XY:

483

AN XY:

713096

show subpopulations

African (AFR)

AF:

0.000156

AC:

AN:

32038

American (AMR)

AF:

0.0000488

AC:

AN:

41014

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25804

East Asian (EAS)

AF:

0.00

AC:

AN:

36238

South Asian (SAS)

AF:

0.0000867

AC:

AN:

80750

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53268

Middle Eastern (MID)

AF:

0.000174

AC:

AN:

5742

European-Non Finnish (NFE)

AF:

0.000858

AC:

945

AN:

1101026

Other (OTH)

AF:

0.000639

AC:

AN:

59474

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

104

157

209

261

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

126

168

210

<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:

0.000401

AC:

AN:

152108

Hom.:

Cov.:

AF XY:

0.000471

AC XY:

AN XY:

74304

show subpopulations

African (AFR)

AF:

0.000145

AC:

AN:

41426

American (AMR)

AF:

0.0000654

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.000208

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00316

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000765

AC:

AN:

68006

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

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:

0.000680

Hom.:

Bravo

AF:

0.000340

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00116

AC:

ExAC

AF:

0.000346

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

0.12

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0089

Eigen

Benign

-0.071

Eigen_PC

Benign

-0.075

FATHMM_MKL

Benign

0.58

LIST_S2

Benign

0.82

M_CAP

Benign

0.0096

MetaRNN

Benign

0.22

MetaSVM

Benign

-1.0

PhyloP100

3.0

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-0.48

REVEL

Benign

0.18

Sift

Uncertain

0.019

Sift4G

Benign

0.25

Polyphen

0.98

Vest4

0.18

MVP

0.66

MPC

0.38

ClinPred

0.066

GERP RS

3.0

Varity_R

0.084

gMVP

0.29

Mutation Taster

=92/8

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