rs747031189

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PP3_Moderate

The NM_032501.4(ACSS1):c.1547G>T(p.Arg516Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000619 in 1,454,328 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

ACSS1
NM_032501.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.69

Publications

0 publications found

Variant links:

Genes affected

ACSS1 (HGNC:16091): (acyl-CoA synthetase short chain family member 1) This gene encodes a mitochondrial acetyl-CoA synthetase enzyme. A similar protein in mice plays an important role in the tricarboxylic acid cycle by catalyzing the conversion of acetate to acetyl CoA. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Nov 2011]

ACSS1 links:

ENSG00000306411 (HGNC:):

ENSG00000306411 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.926

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACSS1	NM_032501.4 link	c.1547G>T	p.Arg516Leu	missense_variant	Exon 10 of 14	ENST00000323482.9	NP_115890.2	Q9NUB1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ACSS1	ENST00000323482.9 link	c.1547G>T	p.Arg516Leu	missense_variant	Exon 10 of 14	1	NM_032501.4	ENSP00000316924.4	Q9NUB1-1
ACSS1	ENST00000432802.6 link	c.1547G>T	p.Arg516Leu	missense_variant	Exon 10 of 12	2		ENSP00000388793.2	Q9NUB1-4
ACSS1	ENST00000537502.5 link	c.1184G>T	p.Arg395Leu	missense_variant	Exon 9 of 13	2		ENSP00000439304.2	Q9NUB1-3
ENSG00000306411	ENST00000818190.1 link	n.503+3964C>A		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000320

AC:

AN:

249760

AF XY:

0.0000370

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000174

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:

0.000328

GnomAD4 exome

AF:

0.00000619

AC:

AN:

1454328

Hom.:

Cov.:

AF XY:

0.00000831

AC XY:

AN XY:

721716

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33364

American (AMR)

AF:

0.000202

AC:

AN:

44558

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26080

East Asian (EAS)

AF:

0.00

AC:

AN:

39426

South Asian (SAS)

AF:

0.00

AC:

AN:

86074

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53162

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5736

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1105932

Other (OTH)

AF:

0.00

AC:

AN:

59996

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.536

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 09, 2022

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.1547G>T (p.R516L) alteration is located in exon 10 (coding exon 10) of the ACSS1 gene. This alteration results from a G to T substitution at nucleotide position 1547, causing the arginine (R) at amino acid position 516 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.47

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Pathogenic

0.14

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.47

.;.;T

Eigen

Uncertain

0.61

Eigen_PC

Uncertain

0.49

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.99

D;D;D

M_CAP

Benign

0.084

MetaRNN

Pathogenic

0.93

D;D;D

MetaSVM

Benign

-0.56

MutationAssessor

Pathogenic

3.4

.;M;M

PhyloP100

5.7

PrimateAI

Uncertain

0.54

PROVEAN

Pathogenic

-6.2

.;D;D

REVEL

Uncertain

0.49

Sift

Uncertain

0.014

.;D;D

Sift4G

Uncertain

0.016

D;D;D

Polyphen

1.0

.;.;D

Vest4

0.86

MutPred

0.76

.;Loss of loop (P = 0.0804);Loss of loop (P = 0.0804);

MVP

0.62

MPC

1.7

ClinPred

0.91

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.81

gMVP

0.84

Mutation Taster

=36/64

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

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rs747031189

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over