Variant 16-20624112-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP6_Moderate

The NM_001318890.3(ACSM1):c.1631A>G(p.Tyr544Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000548 in 1,460,432 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

ACSM1
NM_001318890.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.37

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:

ACSM1 (HGNC:):

ACSM1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP6

Variant 16-20624112-T-C is Benign according to our data. Variant chr16-20624112-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2624154.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACSM1	NM_001318890.3 linkuse as main transcript	c.1631A>G	p.Tyr544Cys	missense_variant	13/14	ENST00000520010.6	NP_001305819.1	Q08AH1-1B2RAP4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACSM1	ENST00000520010.6 linkuse as main transcript	c.1631A>G	p.Tyr544Cys	missense_variant	13/14	1	NM_001318890.3	ENSP00000428047.1		Q08AH1-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251448

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135892

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000548

AC:

AN:

1460432

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726530

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 14, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.60

BayesDel_addAF

Benign

-0.028

BayesDel_noAF

Benign

-0.18

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.27

T;T

Eigen

Benign

0.065

Eigen_PC

Benign

-0.15

FATHMM_MKL

Benign

0.72

LIST_S2

Uncertain

0.93

.;D

M_CAP

Benign

0.0098

MetaRNN

Uncertain

0.64

D;D

MetaSVM

Uncertain

0.11

MutationAssessor

Pathogenic

3.9

H;H

PrimateAI

Uncertain

0.64

PROVEAN

Pathogenic

-7.9

D;D

REVEL

Uncertain

0.34

Sift

Uncertain

0.0010

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;D

Vest4

0.42

MutPred

0.55

Gain of catalytic residue at P543 (P = 0.0157);Gain of catalytic residue at P543 (P = 0.0157);

MVP

0.74

MPC

0.48

ClinPred

0.99

GERP RS

2.8

Varity_R

0.77

gMVP

0.29

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over