Genetic Variant ACSS2:p.Arg52Pro (chr20-34876800-G-C) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_018677.4(ACSS2):c.155G>C(p.Arg52Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000393 in 1,322,074 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000022 ( 0 hom. )

Consequence

ACSS2
NM_018677.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.43

Publications

0 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.37598416).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018677.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ACSS2	NM_018677.4	MANE Select	c.155G>C	p.Arg52Pro	missense	Exon 1 of 18	NP_061147.1	Q9NR19-1
ACSS2	NM_001076552.3		c.155G>C	p.Arg52Pro	missense	Exon 1 of 19	NP_001070020.2	Q9NR19-2
ACSS2	NM_001242393.2		c.-108+1663G>C		intron	N/A	NP_001229322.1	Q4G0E8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ACSS2	ENST00000360596.7	TSL:1 MANE Select	c.155G>C	p.Arg52Pro	missense	Exon 1 of 18	ENSP00000353804.2	Q9NR19-1
ACSS2	ENST00000484354.1	TSL:5	c.155G>C	p.Arg52Pro	missense	Exon 1 of 3	ENSP00000419167.1	C9JXD9
ACSS2	ENST00000871370.1		c.155G>C	p.Arg52Pro	missense	Exon 1 of 20	ENSP00000541429.1

Frequencies

GnomAD3 genomes

AF:

0.000164

AC:

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000603

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

10332

AF XY:

0.00

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000222

AC:

AN:

1169770

Hom.:

Cov.:

AF XY:

0.0000231

AC XY:

AN XY:

562028

show subpopulations

African (AFR)

AF:

0.000809

AC:

AN:

23472

American (AMR)

AF:

0.00

AC:

AN:

9428

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16108

East Asian (EAS)

AF:

0.00

AC:

AN:

26736

South Asian (SAS)

AF:

0.00

AC:

AN:

43090

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37518

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3150

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

963116

Other (OTH)

AF:

0.000148

AC:

AN:

47152

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.000171

AC:

AN:

152304

Hom.:

Cov.:

AF XY:

0.000201

AC XY:

AN XY:

74470

show subpopulations

African (AFR)

AF:

0.000625

AC:

AN:

41584

American (AMR)

AF:

0.00

AC:

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5164

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67998

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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:

0.00

Hom.:

Bravo

AF:

0.000219

ExAC

AF:

0.0000363

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Pathogenic

0.81

BayesDel_addAF

Uncertain

0.055

BayesDel_noAF

Benign

-0.16

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.62

Eigen

Uncertain

0.36

Eigen_PC

Uncertain

0.32

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.78

M_CAP

Benign

0.074

MetaRNN

Benign

0.38

MetaSVM

Benign

-0.65

MutationAssessor

Uncertain

2.4

PhyloP100

1.4

PrimateAI

Uncertain

0.67

PROVEAN

Uncertain

-2.5

REVEL

Benign

0.28

Sift

Uncertain

0.020

Sift4G

Uncertain

0.030

Polyphen

0.72

Vest4

0.42

MutPred

0.47

Loss of MoRF binding (P = 0.0047)

MVP

0.58

MPC

2.5

ClinPred

0.98

GERP RS

3.4

PromoterAI

-0.025

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.75

gMVP

0.81

Mutation Taster

=81/19

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