Genetic Variant ACSS3:p.Pro22His (chr12-81078185-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001330243.2(ACSS3):c.-941C>A variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000574 in 1,394,388 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: not found (cov: 31)

Exomes 𝑓: 0.0000057 ( 0 hom. )

Consequence

ACSS3
NM_001330243.2 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.34

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1997056).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001330243.2. 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.65C>A	p.Pro22His	missense	Exon 1 of 16	NP_078836.1	Q9H6R3-1
ACSS3	NM_001330243.2		c.-941C>A		5_prime_UTR_premature_start_codon_gain	Exon 1 of 17	NP_001317172.1	Q9H6R3-2
ACSS3	NM_001330242.2		c.65C>A	p.Pro22His	missense	Exon 1 of 16	NP_001317171.1	A0A0B4J1R2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ACSS3	ENST00000548058.6	TSL:1 MANE Select	c.65C>A	p.Pro22His	missense	Exon 1 of 16	ENSP00000449535.1	Q9H6R3-1
ACSS3	ENST00000261206.7	TSL:1	c.65C>A	p.Pro22His	missense	Exon 1 of 16	ENSP00000261206.3	A0A0B4J1R2
ACSS3	ENST00000965760.1		c.65C>A	p.Pro22His	missense	Exon 1 of 16	ENSP00000635819.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

153186

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:

0.00000574

AC:

AN:

1394388

Hom.:

Cov.:

AF XY:

0.00000580

AC XY:

AN XY:

689770

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30684

American (AMR)

AF:

0.00

AC:

AN:

30490

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24220

East Asian (EAS)

AF:

0.00

AC:

AN:

36602

South Asian (SAS)

AF:

0.00

AC:

AN:

80958

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46088

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5380

European-Non Finnish (NFE)

AF:

0.00000647

AC:

AN:

1082470

Other (OTH)

AF:

0.0000174

AC:

AN:

57496

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

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

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000172

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

0.11

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

Eigen

Benign

-0.093

Eigen_PC

Benign

-0.032

FATHMM_MKL

Benign

0.48

LIST_S2

Benign

0.68

M_CAP

Benign

0.060

MetaRNN

Benign

0.20

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

PhyloP100

2.3

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-0.16

REVEL

Benign

0.053

Sift

Uncertain

0.0090

Sift4G

Uncertain

0.019

Polyphen

0.71

Vest4

0.29

MutPred

0.30

Loss of glycosylation at P22 (P = 0.025)

MVP

0.19

MPC

0.83

ClinPred

0.73

GERP RS

3.7

PromoterAI

-0.20

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.12

gMVP

0.56

Mutation Taster

=94/6

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over