17-45137109-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001135705.3(ACBD4):​c.385C>T​(p.Pro129Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000192 in 1,613,996 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: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

ACBD4
NM_001135705.3 missense

Scores

2
5
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.89
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.26831743).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ACBD4NM_001135705.3 linkc.385C>T p.Pro129Ser missense_variant 5/10 ENST00000321854.13 NP_001129177.1 Q8NC06-2A0A0S2Z5Q0

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ACBD4ENST00000321854.13 linkc.385C>T p.Pro129Ser missense_variant 5/101 NM_001135705.3 ENSP00000314440.8 Q8NC06-2
ACBD4ENST00000591859.5 linkc.385C>T p.Pro129Ser missense_variant 7/121 ENSP00000465610.1 Q8NC06-3

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152176
Hom.:
0
Cov.:
33
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:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000200
AC:
5
AN:
249390
Hom.:
0
AF XY:
0.0000148
AC XY:
2
AN XY:
135354
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:
0.0000353
Gnomad OTH exome
AF:
0.000165
GnomAD4 exome
AF:
0.0000205
AC:
30
AN:
1461820
Hom.:
0
Cov.:
32
AF XY:
0.0000220
AC XY:
16
AN XY:
727222
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
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:
0.0000243
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152176
Hom.:
0
Cov.:
33
AF XY:
0.0000135
AC XY:
1
AN XY:
74340
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000624
Hom.:
0
Bravo
AF:
0.0000113
ExAC
AF:
0.00000827
AC:
1
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

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 submitterclinical testingAmbry GeneticsAug 02, 2023The c.385C>T (p.P129S) alteration is located in exon 7 (coding exon 4) of the ACBD4 gene. This alteration results from a C to T substitution at nucleotide position 385, causing the proline (P) at amino acid position 129 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
0.95
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.37
CADD
Pathogenic
28
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.014
T;.;.;.;.;T;T;.
Eigen
Uncertain
0.61
Eigen_PC
Uncertain
0.62
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.93
D;D;.;.;.;D;.;D
M_CAP
Benign
0.014
T
MetaRNN
Benign
0.27
T;T;T;T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.4
M;M;M;M;M;.;M;M
PrimateAI
Benign
0.47
T
PROVEAN
Benign
-2.1
.;N;.;.;N;.;N;N
REVEL
Benign
0.11
Sift
Benign
0.040
.;D;.;.;T;.;T;D
Sift4G
Benign
0.53
T;D;D;D;T;T;T;T
Polyphen
1.0
D;P;P;P;D;.;D;D
Vest4
0.47
MutPred
0.32
Loss of catalytic residue at P129 (P = 0.0012);Loss of catalytic residue at P129 (P = 0.0012);Loss of catalytic residue at P129 (P = 0.0012);Loss of catalytic residue at P129 (P = 0.0012);Loss of catalytic residue at P129 (P = 0.0012);Loss of catalytic residue at P129 (P = 0.0012);Loss of catalytic residue at P129 (P = 0.0012);Loss of catalytic residue at P129 (P = 0.0012);
MVP
0.43
MPC
0.47
ClinPred
0.81
D
GERP RS
4.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.18
gMVP
0.59

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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.

Other links and lift over

dbSNP: rs753494123; hg19: chr17-43214476; API