Variant chr20-25013978-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_032501.4(ACSS1):c.1435G>A(p.Val479Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00315 in 1,613,688 control chromosomes in the GnomAD database, including 126 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.015 ( 65 hom., cov: 33)

Exomes 𝑓: 0.0019 ( 61 hom. )

Consequence

ACSS1
NM_032501.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.49

Variant links:

Genes affected

ACSS1 (HGNC:16091): (acyl-CoA synthetase short chain family member 1) This gene encodes a mitochondrial acetyl-CoA synthetase enzyme. A similar protein in mice plays an important role in the tricarboxylic acid cycle by catalyzing the conversion of acetate to acetyl CoA. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Nov 2011]

ACSS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.01578024).

BP6

Variant 20-25013978-C-T is Benign according to our data. Variant chr20-25013978-C-T is described in ClinVar as [Benign]. Clinvar id is 1258805.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0536 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACSS1	NM_032501.4 linkuse as main transcript	c.1435G>A	p.Val479Ile	missense_variant	9/14	ENST00000323482.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACSS1	ENST00000323482.9 linkuse as main transcript	c.1435G>A	p.Val479Ile	missense_variant	9/14	1	NM_032501.4	P1	Q9NUB1-1
ACSS1	ENST00000432802.6 linkuse as main transcript	c.1435G>A	p.Val479Ile	missense_variant	9/12	2			Q9NUB1-4
ACSS1	ENST00000537502.5 linkuse as main transcript	c.1072G>A	p.Val358Ile	missense_variant	8/13	2			Q9NUB1-3

Frequencies

GnomAD3 genomes

AF:

0.0150

AC:

2279

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0514

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00602

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000338

Gnomad OTH

AF:

0.0115

GnomAD3 exomes

AF:

0.00447

AC:

1117

AN:

249968

Hom.:

AF XY:

0.00351

AC XY:

475

AN XY:

135254

show subpopulations

Gnomad AFR exome

AF:

0.0536

Gnomad AMR exome

AF:

0.00499

Gnomad ASJ exome

AF:

0.000497

Gnomad EAS exome

AF:

0.0000545

Gnomad SAS exome

AF:

0.000295

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000398

Gnomad OTH exome

AF:

0.00360

GnomAD4 exome

AF:

0.00192

AC:

2801

AN:

1461354

Hom.:

Cov.:

AF XY:

0.00178

AC XY:

1292

AN XY:

726952

show subpopulations

Gnomad4 AFR exome

AF:

0.0557

Gnomad4 AMR exome

AF:

0.00526

Gnomad4 ASJ exome

AF:

0.0000766

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000255

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000263

Gnomad4 OTH exome

AF:

0.00548

GnomAD4 genome

AF:

0.0150

AC:

2286

AN:

152334

Hom.:

Cov.:

AF XY:

0.0148

AC XY:

1105

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.0514

Gnomad4 AMR

AF:

0.00601

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000338

Gnomad4 OTH

AF:

0.0113

Alfa

AF:

0.00195

Hom.:

Bravo

AF:

0.0178

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0517

AC:

228

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.00527

AC:

640

Asia WGS

AF:

0.00722

AC:

AN:

3478

EpiCase

AF:

0.000545

EpiControl

AF:

0.000534

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.64

CADD

Benign

8.9

DANN

Uncertain

0.98

DEOGEN2

Benign

0.11

.;.;T

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.61

FATHMM_MKL

Benign

0.27

LIST_S2

Benign

0.79

T;T;T

MetaRNN

Benign

0.016

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.2

.;M;M

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.94

.;N;N

REVEL

Benign

0.11

Sift

Benign

0.036

.;D;D

Sift4G

Benign

0.11

T;T;T

Polyphen

0.92

.;.;P

Vest4

0.20

MVP

0.26

MPC

0.51

ClinPred

0.0098

GERP RS

2.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.17

gMVP

0.47

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