Variant 12-81078292-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_024560.4(ACSS3):c.172A>G(p.Ser58Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000986 in 1,611,912 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000099 ( 0 hom. )

Consequence

ACSS3
NM_024560.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0470

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.030920208).

BP6

Variant 12-81078292-A-G is Benign according to our data. Variant chr12-81078292-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2263157.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACSS3	NM_024560.4 linkuse as main transcript	c.172A>G	p.Ser58Gly	missense_variant	1/16	ENST00000548058.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACSS3	ENST00000548058.6 linkuse as main transcript	c.172A>G	p.Ser58Gly	missense_variant	1/16	1	NM_024560.4	A1	Q9H6R3-1
ACSS3	ENST00000261206.7 linkuse as main transcript	c.172A>G	p.Ser58Gly	missense_variant	1/16	1		P4
ACSS3	ENST00000549175.1 linkuse as main transcript	c.-13-31268A>G		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0000922

AC:

AN:

151922

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000782

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000907

AC:

AN:

242584

Hom.:

AF XY:

0.0000602

AC XY:

AN XY:

132812

show subpopulations

Gnomad AFR exome

AF:

0.0000672

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000386

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000130

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000993

AC:

145

AN:

1459872

Hom.:

Cov.:

AF XY:

0.0000950

AC XY:

AN XY:

726230

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000353

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000111

Gnomad4 OTH exome

AF:

0.000133

GnomAD4 genome

AF:

0.0000921

AC:

AN:

152040

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000783

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000133

Hom.:

Bravo

AF:

0.0000869

ESP6500AA

AF:

0.000241

AC:

ESP6500EA

AF:

0.000244

AC:

ExAC

AF:

0.0000501

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 01, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.053

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.68

CADD

Benign

DANN

Benign

0.39

DEOGEN2

Benign

0.17

T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.0066

LIST_S2

Benign

0.35

T;T

M_CAP

Benign

0.015

MetaRNN

Benign

0.031

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.27

N;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.98

N;N

REVEL

Benign

0.019

Sift

Benign

0.55

T;T

Sift4G

Benign

0.16

T;T

Polyphen

0.0

B;.

Vest4

0.094

MVP

0.030

MPC

0.18

ClinPred

0.0085

GERP RS

0.033

Varity_R

0.049

gMVP

0.31

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