Genetic Variant ACSM1:p.Val400Leu (chr16-20636840-C-G) – 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_001318890.3(ACSM1):c.1198G>C(p.Val400Leu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/26 in silico tools predict a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. 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. V400I) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Consequence

ACSM1
NM_001318890.3 missense, splice_region

Scores

Splicing: ADA: 0.01666

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.590

Publications

1 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: 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=0.1901795).

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.1198G>C	p.Val400Leu	missense splice_region	Exon 10 of 14	NP_001305819.1	Q08AH1-1
ACSM1	NM_052956.3		c.1198G>C	p.Val400Leu	missense splice_region	Exon 9 of 13	NP_443188.2	Q08AH1-1
ACSM1	NR_134918.2		n.1202+531G>C		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ACSM1	ENST00000520010.6	TSL:1 MANE Select	c.1198G>C	p.Val400Leu	missense splice_region	Exon 10 of 14	ENSP00000428047.1	Q08AH1-1
ACSM1	ENST00000307493.8	TSL:1	c.1198G>C	p.Val400Leu	missense splice_region	Exon 9 of 13	ENSP00000301956.3	Q08AH1-1
ACSM1	ENST00000519745.5	TSL:1	n.*519+531G>C		intron	N/A	ENSP00000428650.1	Q08AH1-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00000418

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.36

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Benign

0.66

DEOGEN2

Benign

0.019

Eigen

Benign

-0.80

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.46

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.0066

MetaRNN

Benign

0.19

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.40

PhyloP100

0.59

PrimateAI

Benign

0.40

PROVEAN

Benign

-1.4

REVEL

Benign

0.053

Sift

Benign

0.11

Sift4G

Benign

0.22

Polyphen

0.12

Vest4

0.41

MutPred

0.63

Loss of methylation at K404 (P = 0.0838)

MVP

0.25

MPC

0.11

ClinPred

0.19

GERP RS

2.4

Varity_R

0.062

gMVP

0.48

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.017

dbscSNV1_RF

Benign

0.20

SpliceAI score (max)

0.33

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.33

Position offset: 0

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over