20-34913468-C-T

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018677.4(ACSS2):c.542C>T(p.Ala181Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00178 in 1,613,898 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00085 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0019 ( 1 hom. )

Consequence

ACSS2
NM_018677.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1B:1

Conservation

PhyloP100: 2.10

Variant links:

Genes affected

ACSS2 (HGNC:15814): (acyl-CoA synthetase short chain family member 2) This gene encodes a cytosolic enzyme that catalyzes the activation of acetate for use in lipid synthesis and energy generation. The protein acts as a monomer and produces acetyl-CoA from acetate in a reaction that requires ATP. Expression of this gene is regulated by sterol regulatory element-binding proteins, transcription factors that activate genes required for the synthesis of cholesterol and unsaturated fatty acids. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2009]

ACSS2 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;

BP4

Computational evidence support a benign effect (MetaRNN=0.07492846).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACSS2	NM_018677.4 link	c.542C>T	p.Ala181Val	missense_variant	Exon 4 of 18	ENST00000360596.7	NP_061147.1	Q9NR19-1Q6DKJ3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACSS2	ENST00000360596.7 link	c.542C>T	p.Ala181Val	missense_variant	Exon 4 of 18	1	NM_018677.4	ENSP00000353804.2		Q9NR19-1

Frequencies

GnomAD3 genomes

AF:

0.000848

AC:

129

AN:

152080

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000435

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:

0.00163

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000833

AC:

209

AN:

250940

Hom.:

AF XY:

0.000796

AC XY:

108

AN XY:

135596

show subpopulations

Gnomad AFR exome

AF:

0.000615

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00169

Gnomad OTH exome

AF:

0.000980

GnomAD4 exome

AF:

0.00187

AC:

2735

AN:

1461700

Hom.:

Cov.:

AF XY:

0.00177

AC XY:

1290

AN XY:

727144

show subpopulations

Gnomad4 AFR exome

AF:

0.000478

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000750

Gnomad4 NFE exome

AF:

0.00239

Gnomad4 OTH exome

AF:

0.000911

GnomAD4 genome

AF:

0.000854

AC:

130

AN:

152198

Hom.:

Cov.:

AF XY:

0.000632

AC XY:

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.000433

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00165

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00134

Hom.:

Bravo

AF:

0.000941

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00151

AC:

ExAC

AF:

0.000675

AC:

EpiCase

AF:

0.00174

EpiControl

AF:

0.00172

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 11, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.542C>T (p.A181V) alteration is located in exon 4 (coding exon 4) of the ACSS2 gene. This alteration results from a C to T substitution at nucleotide position 542, causing the alanine (A) at amino acid position 181 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

ACSS2-related disorder

Benign:1

May 28, 2024

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.16

T;T;T;.

Eigen

Uncertain

0.22

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Uncertain

0.93

LIST_S2

Pathogenic

0.99

D;D;D;D

M_CAP

Benign

0.023

MetaRNN

Benign

0.075

T;T;T;T

MetaSVM

Benign

-0.57

MutationAssessor

Uncertain

2.5

.;M;.;M

PrimateAI

Uncertain

0.65

PROVEAN

Uncertain

-3.4

D;D;D;D

REVEL

Benign

0.19

Sift

Uncertain

0.013

D;D;D;D

Sift4G

Uncertain

0.021

D;D;D;D

Polyphen

0.53

.;P;.;.

Vest4

0.39, 0.38

MVP

0.41

MPC

0.34

ClinPred

0.11

GERP RS

4.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.21

gMVP

0.54

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

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