Variant 15-78173784-A-G 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_015162.5(ACSBG1):c.1898T>C(p.Met633Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,866 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M633V) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ACSBG1
NM_015162.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.89

Variant links:

Genes affected

ACSBG1 (HGNC:29567): (acyl-CoA synthetase bubblegum family member 1) The protein encoded by this gene possesses long-chain acyl-CoA synthetase activity. It is thought to play a central role in brain very long-chain fatty acids metabolism and myelinogenesis. [provided by RefSeq, Jul 2008]

ACSBG1 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=0.12681052).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACSBG1	NM_015162.5 linkuse as main transcript	c.1898T>C	p.Met633Thr	missense_variant	13/14	ENST00000258873.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
ACSBG1	ENST00000258873.9 linkuse as main transcript	c.1898T>C	p.Met633Thr	missense_variant	13/14	1	NM_015162.5	P1
ACSBG1	ENST00000560817.5 linkuse as main transcript	c.1172T>C	p.Met391Thr	missense_variant	9/10	5
ACSBG1	ENST00000560183.1 linkuse as main transcript	n.484T>C		non_coding_transcript_exon_variant	2/2	2
ACSBG1	ENST00000560124.5 linkuse as main transcript	c.*1210T>C		3_prime_UTR_variant, NMD_transcript_variant	9/10	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251262

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135802

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:

0.00000880

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461866

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727242

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:

0.0000374

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000165

AC:

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

Aug 04, 2021

The c.1898T>C (p.M633T) alteration is located in exon 13 (coding exon 13) of the ACSBG1 gene. This alteration results from a T to C substitution at nucleotide position 1898, causing the methionine (M) at amino acid position 633 to be replaced by a threonine (T). 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

0.082

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.58

Cadd

Benign

Dann

Benign

0.94

DEOGEN2

Benign

0.26

T;T

Eigen

Benign

-0.23

Eigen_PC

Benign

0.015

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.23

T;T

M_CAP

Benign

0.0060

MetaRNN

Benign

0.13

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.20

N;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.25

PROVEAN

Benign

-1.7

N;N

REVEL

Benign

0.057

Sift

Benign

0.061

T;T

Sift4G

Uncertain

0.051

T;T

Polyphen

0.0

B;.

Vest4

0.19

MutPred

0.41

Loss of catalytic residue at M633 (P = 0.0295);.;

MVP

0.41

MPC

0.38

ClinPred

0.37

GERP RS

5.3

Varity_R

0.16

gMVP

0.65

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