dbSNP rs770014944: ACSS3:p.Pro136Ala (chr12-81109654-C-G) – 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_024560.4(ACSS3):c.406C>G(p.Pro136Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000739 in 1,610,810 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 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000070 ( 0 hom. )

Consequence

ACSS3
NM_024560.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.37

Publications

4 publications found

Variant links:

Genes affected

ACSS3 (HGNC:24723): (acyl-CoA synthetase short chain family member 3) Enables propionate-CoA ligase activity. Predicted to be involved in ketone body biosynthetic process. Located in mitochondrial matrix. [provided by Alliance of Genome Resources, Apr 2022]

ACSS3 links:

ACSS3-AS1 (HGNC:58286):

ACSS3-AS1 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=0.2983905).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024560.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ACSS3	NM_024560.4	MANE Select	c.406C>G	p.Pro136Ala	missense	Exon 2 of 16	NP_078836.1	Q9H6R3-1
ACSS3	NM_001330242.2		c.403C>G	p.Pro135Ala	missense	Exon 2 of 16	NP_001317171.1	A0A0B4J1R2
ACSS3	NM_001330243.2		c.-600C>G		5_prime_UTR	Exon 2 of 17	NP_001317172.1	Q9H6R3-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ACSS3	ENST00000548058.6	TSL:1 MANE Select	c.406C>G	p.Pro136Ala	missense	Exon 2 of 16	ENSP00000449535.1	Q9H6R3-1
ACSS3	ENST00000261206.7	TSL:1	c.403C>G	p.Pro135Ala	missense	Exon 2 of 16	ENSP00000261206.3	A0A0B4J1R2
ACSS3	ENST00000965760.1		c.406C>G	p.Pro136Ala	missense	Exon 2 of 16	ENSP00000635819.1

Frequencies

GnomAD3 genomes

AF:

0.000112

AC:

AN:

152114

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000590

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:

0.000103

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000124

AC:

AN:

249272

AF XY:

0.000111

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000679

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000619

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.0000699

AC:

102

AN:

1458696

Hom.:

Cov.:

AF XY:

0.0000634

AC XY:

AN XY:

725520

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33390

American (AMR)

AF:

0.000563

AC:

AN:

44416

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26082

East Asian (EAS)

AF:

0.00

AC:

AN:

39508

South Asian (SAS)

AF:

0.00

AC:

AN:

85400

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53346

Middle Eastern (MID)

AF:

0.000530

AC:

AN:

5664

European-Non Finnish (NFE)

AF:

0.0000648

AC:

AN:

1110628

Other (OTH)

AF:

0.0000332

AC:

AN:

60262

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.446

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:

0.000112

AC:

AN:

152114

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74296

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41428

American (AMR)

AF:

0.000590

AC:

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000103

AC:

AN:

68012

Other (OTH)

AF:

0.000478

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

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:

0.0000752

Hom.:

Bravo

AF:

0.0000869

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.000107

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

0.15

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.18

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.27

Eigen

Pathogenic

0.75

Eigen_PC

Pathogenic

0.79

FATHMM_MKL

Uncertain

0.97

LIST_S2

Pathogenic

0.99

M_CAP

Benign

0.024

MetaRNN

Benign

0.30

MetaSVM

Benign

-0.77

MutationAssessor

Benign

1.4

PhyloP100

5.4

PrimateAI

Uncertain

0.65

PROVEAN

Pathogenic

-7.6

REVEL

Benign

0.27

Sift

Benign

0.089

Sift4G

Benign

0.11

Polyphen

1.0

Vest4

0.79

MVP

0.55

MPC

0.76

ClinPred

0.31

GERP RS

6.1

Varity_R

0.37

gMVP

0.66

Mutation Taster

=22/78

disease causing

(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