Genetic Variant ACSS2:p.Trp29Ser (chr20-34876731-G-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_018677.4(ACSS2):c.86G>C(p.Trp29Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000568 in 1,441,188 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. W29C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00034 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00060 ( 0 hom. )

Consequence

ACSS2
NM_018677.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.55

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 -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.12979665).

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.86G>C	p.Trp29Ser	missense	Exon 1 of 18	NP_061147.1	Q9NR19-1
ACSS2	NM_001076552.3		c.86G>C	p.Trp29Ser	missense	Exon 1 of 19	NP_001070020.2	Q9NR19-2
ACSS2	NM_001242393.2		c.-108+1594G>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.86G>C	p.Trp29Ser	missense	Exon 1 of 18	ENSP00000353804.2	Q9NR19-1
ACSS2	ENST00000484354.1	TSL:5	c.86G>C	p.Trp29Ser	missense	Exon 1 of 3	ENSP00000419167.1	C9JXD9
ACSS2	ENST00000871370.1		c.86G>C	p.Trp29Ser	missense	Exon 1 of 20	ENSP00000541429.1

Frequencies

GnomAD3 genomes

AF:

0.000348

AC:

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000588

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000201

AC:

AN:

79750

AF XY:

0.000177

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000376

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000595

AC:

767

AN:

1288866

Hom.:

Cov.:

AF XY:

0.000590

AC XY:

372

AN XY:

630144

show subpopulations

African (AFR)

AF:

0.000193

AC:

AN:

25860

American (AMR)

AF:

0.0000436

AC:

AN:

22936

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22340

East Asian (EAS)

AF:

0.00

AC:

AN:

27736

South Asian (SAS)

AF:

0.000371

AC:

AN:

67344

European-Finnish (FIN)

AF:

0.0000217

AC:

AN:

46140

Middle Eastern (MID)

AF:

0.000268

AC:

AN:

3738

European-Non Finnish (NFE)

AF:

0.000712

AC:

726

AN:

1020372

Other (OTH)

AF:

0.000153

AC:

AN:

52400

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

121

162

202

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

120

150

<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:

0.000341

AC:

AN:

152322

Hom.:

Cov.:

AF XY:

0.000309

AC XY:

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.000240

AC:

AN:

41594

American (AMR)

AF:

0.0000653

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5150

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000588

AC:

AN:

68018

Other (OTH)

AF:

0.000473

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

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:

0.000103

Hom.:

Bravo

AF:

0.000363

ExAC

AF:

0.000116

AC:

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

Benign

0.13

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.13

CADD

Uncertain

(source)

DANN

Benign

0.96

DEOGEN2

Uncertain

0.47

Eigen

Benign

0.014

Eigen_PC

Benign

0.12

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.85

M_CAP

Benign

0.029

MetaRNN

Benign

0.13

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

PhyloP100

1.6

PrimateAI

Uncertain

0.73

PROVEAN

Uncertain

-2.5

REVEL

Benign

0.26

Sift

Benign

0.034

Sift4G

Uncertain

0.050

Polyphen

0.82

Vest4

0.29

MutPred

0.44

Gain of phosphorylation at W29 (P = 0.0017)

MVP

0.55

MPC

2.8

ClinPred

0.14

GERP RS

4.0

PromoterAI

0.023

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.34

gMVP

0.69

Mutation Taster

=83/17

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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