Variant 17-41886139-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM1BP4_ModerateBP6_ModerateBS2

The NM_001096.3(ACLY):c.2045A>G(p.Tyr682Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000893 in 1,614,062 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00087 ( 0 hom. )

Consequence

ACLY
NM_001096.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.60

Variant links:

Genes affected

ACLY (HGNC:115): (ATP citrate lyase) ATP citrate lyase is the primary enzyme responsible for the synthesis of cytosolic acetyl-CoA in many tissues. The enzyme is a tetramer (relative molecular weight approximately 440,000) of apparently identical subunits. It catalyzes the formation of acetyl-CoA and oxaloacetate from citrate and CoA with a concomitant hydrolysis of ATP to ADP and phosphate. The product, acetyl-CoA, serves several important biosynthetic pathways, including lipogenesis and cholesterogenesis. In nervous tissue, ATP citrate-lyase may be involved in the biosynthesis of acetylcholine. Multiple transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Dec 2014]

ACLY links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

PM1

In a modified_residue Phosphotyrosine (size 0) in uniprot entity ACLY_HUMAN

BP4

Computational evidence support a benign effect (MetaRNN=0.0771403).

BP6

Variant 17-41886139-T-C is Benign according to our data. Variant chr17-41886139-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 731742.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 166 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACLY	NM_001096.3 linkuse as main transcript	c.2045A>G	p.Tyr682Cys	missense_variant	18/29	ENST00000352035.7	NP_001087.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACLY	ENST00000352035.7 linkuse as main transcript	c.2045A>G	p.Tyr682Cys	missense_variant	18/29	1	NM_001096.3	ENSP00000253792	P3	P53396-1

Frequencies

GnomAD3 genomes

AF:

0.00109

AC:

166

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000659

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00198

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00107

AC:

268

AN:

251398

Hom.:

AF XY:

0.00101

AC XY:

137

AN XY:

135860

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00496

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000554

Gnomad NFE exome

AF:

0.00174

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.000872

AC:

1275

AN:

1461750

Hom.:

Cov.:

AF XY:

0.000869

AC XY:

632

AN XY:

727170

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

Gnomad4 AMR exome

AF:

0.000246

Gnomad4 ASJ exome

AF:

0.00524

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000861

Gnomad4 NFE exome

AF:

0.000918

Gnomad4 OTH exome

AF:

0.000894

GnomAD4 genome

AF:

0.00109

AC:

166

AN:

152312

Hom.:

Cov.:

AF XY:

0.00103

AC XY:

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.00346

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000659

Gnomad4 NFE

AF:

0.00198

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00153

Hom.:

Bravo

AF:

0.000665

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00105

AC:

ExAC

AF:

0.00119

AC:

145

EpiCase

AF:

0.000927

EpiControl

AF:

0.000948

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Aug 16, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Uncertain

-0.030

CADD

Uncertain

DANN

Benign

0.97

DEOGEN2

Uncertain

0.49

T;T;.;.;.

Eigen

Benign

-0.065

Eigen_PC

Benign

0.017

FATHMM_MKL

Uncertain

0.88

LIST_S2

Pathogenic

0.98

.;D;D;D;.

M_CAP

Uncertain

0.14

MetaRNN

Benign

0.077

T;T;T;T;T

MetaSVM

Uncertain

-0.12

MutationAssessor

Benign

1.5

L;L;.;.;.

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Pathogenic

0.86

PROVEAN

Pathogenic

-6.6

D;.;D;D;D

REVEL

Uncertain

0.56

Sift

Benign

0.063

T;.;T;T;T

Sift4G

Benign

0.10

T;T;T;T;T

Polyphen

0.99

D;D;.;.;.

Vest4

0.85

MVP

0.73

MPC

1.4

ClinPred

0.21

GERP RS

4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.77

gMVP

0.93

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