Variant 17-45137421-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001135705.3(ACBD4):c.469T>C(p.Cys157Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000116 in 1,461,842 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

ACBD4
NM_001135705.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.105

Variant links:

Genes affected

ACBD4 (HGNC:23337): (acyl-CoA binding domain containing 4) This gene encodes a member of the acyl-coenzyme A binding domain containing protein family. All family members contain the conserved acyl-Coenzyme A binding domain, which binds acyl-CoA thiol esters. They are thought to play roles in acyl-CoA dependent lipid metabolism. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2008]

ACBD4 links:

ACBD4 (HGNC:):

ACBD4 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08580971).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACBD4	NM_001135705.3 linkuse as main transcript	c.469T>C	p.Cys157Arg	missense_variant	6/10	ENST00000321854.13	NP_001129177.1	Q8NC06-2A0A0S2Z5Q0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACBD4	ENST00000321854.13 linkuse as main transcript	c.469T>C	p.Cys157Arg	missense_variant	6/10	1	NM_001135705.3	ENSP00000314440.8		Q8NC06-2
ACBD4	ENST00000591859.5 linkuse as main transcript	c.469T>C	p.Cys157Arg	missense_variant	8/12	1		ENSP00000465610.1		Q8NC06-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000401

AC:

AN:

249364

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135366

show subpopulations

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000884

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000116

AC:

AN:

1461842

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

727226

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000153

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 10, 2024

The c.469T>C (p.C157R) alteration is located in exon 8 (coding exon 5) of the ACBD4 gene. This alteration results from a T to C substitution at nucleotide position 469, causing the cysteine (C) at amino acid position 157 to be replaced by an arginine (R). 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

Benign

0.088

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.79

DEOGEN2

Benign

0.0051

T;.;.;.;.;T;T;.

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.84

FATHMM_MKL

Benign

0.061

LIST_S2

Benign

0.56

T;T;.;.;.;T;.;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.086

T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

L;L;L;L;L;.;L;L

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.59

.;N;.;.;N;.;N;N

REVEL

Benign

0.033

Sift

Benign

0.15

.;T;.;.;T;.;T;T

Sift4G

Benign

0.71

T;T;T;T;T;T;T;T

Polyphen

0.74

P;P;P;P;B;.;P;B

Vest4

0.23

MutPred

0.15

Loss of catalytic residue at P156 (P = 0.0248);Loss of catalytic residue at P156 (P = 0.0248);Loss of catalytic residue at P156 (P = 0.0248);Loss of catalytic residue at P156 (P = 0.0248);Loss of catalytic residue at P156 (P = 0.0248);Loss of catalytic residue at P156 (P = 0.0248);Loss of catalytic residue at P156 (P = 0.0248);Loss of catalytic residue at P156 (P = 0.0248);

MVP

0.34

MPC

0.89

ClinPred

0.14

GERP RS

0.85

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.18

gMVP

0.42

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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