Variant 17-45136511-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001135705.3(ACBD4):c.100C>T(p.Pro34Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000428 in 1,613,152 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000043 ( 1 hom. )

Consequence

ACBD4
NM_001135705.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.29

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACBD4	NM_001135705.3 link	c.100C>T	p.Pro34Ser	missense_variant	3/10	ENST00000321854.13	NP_001129177.1	Q8NC06-2A0A0S2Z5Q0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACBD4	ENST00000321854.13 link	c.100C>T	p.Pro34Ser	missense_variant	3/10	1	NM_001135705.3	ENSP00000314440.8		Q8NC06-2
ACBD4	ENST00000591859.5 link	c.100C>T	p.Pro34Ser	missense_variant	5/12	1		ENSP00000465610.1		Q8NC06-3

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000963

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000523

AC:

AN:

248580

Hom.:

AF XY:

0.0000593

AC XY:

AN XY:

134908

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000724

Gnomad SAS 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:

0.0000431

AC:

AN:

1460830

Hom.:

Cov.:

AF XY:

0.0000482

AC XY:

AN XY:

726744

show subpopulations

Gnomad4 AFR exome

AF:

0.000478

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000453

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.000464

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152322

Hom.:

Cov.:

AF XY:

0.0000671

AC XY:

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000966

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.0000340

ExAC

AF:

0.0000662

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

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

Jan 17, 2024

The c.100C>T (p.P34S) alteration is located in exon 5 (coding exon 2) of the ACBD4 gene. This alteration results from a C to T substitution at nucleotide position 100, causing the proline (P) at amino acid position 34 to be replaced by a serine (S). 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

Pathogenic

0.97

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Uncertain

-0.030

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.076

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

Eigen

Uncertain

0.67

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Uncertain

0.82

LIST_S2

Uncertain

0.95

D;D;.;.;.;D;.;D

M_CAP

Benign

0.016

MetaRNN

Uncertain

0.58

D;D;D;D;D;D;D;D

MetaSVM

Benign

-0.76

MutationAssessor

Pathogenic

3.1

M;M;M;M;M;.;M;M

PrimateAI

Uncertain

0.58

PROVEAN

Pathogenic

-7.0

.;D;.;.;D;.;D;D

REVEL

Benign

0.24

Sift

Benign

0.033

.;D;.;.;D;.;D;D

Sift4G

Uncertain

0.0040

D;D;D;D;D;D;D;D

Polyphen

1.0

D;P;P;P;D;.;D;D

Vest4

0.82

MutPred

0.67

Gain of phosphorylation at P34 (P = 0.0349);Gain of phosphorylation at P34 (P = 0.0349);Gain of phosphorylation at P34 (P = 0.0349);Gain of phosphorylation at P34 (P = 0.0349);Gain of phosphorylation at P34 (P = 0.0349);Gain of phosphorylation at P34 (P = 0.0349);Gain of phosphorylation at P34 (P = 0.0349);Gain of phosphorylation at P34 (P = 0.0349);

MVP

0.44

MPC

0.64

ClinPred

0.72

GERP RS

4.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.67

gMVP

0.71

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