Variant 16-20545254-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001105069.2(ACSM2B):c.1184T>C(p.Ile395Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000685 in 1,460,848 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

ACSM2B
NM_001105069.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.57

Variant links:

Genes affected

ACSM2B (HGNC:30931): (acyl-CoA synthetase medium chain family member 2B) Enables benzoate-CoA ligase activity. Predicted to be involved in acyl-CoA metabolic process and fatty acid biosynthetic process. Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

ACSM2B links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.895

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ACSM2B	NM_001105069.2 linkuse as main transcript	c.1184T>C	p.Ile395Thr	missense_variant	10/14	ENST00000329697.10
ACSM2B	NM_182617.4 linkuse as main transcript	c.1184T>C	p.Ile395Thr	missense_variant	11/15
ACSM2B	NM_001410902.1 linkuse as main transcript	c.947T>C	p.Ile316Thr	missense_variant	9/13
ACSM2B	XR_001751899.3 linkuse as main transcript	n.1353T>C		non_coding_transcript_exon_variant	10/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACSM2B	ENST00000329697.10 linkuse as main transcript	c.1184T>C	p.Ile395Thr	missense_variant	10/14	1	NM_001105069.2	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250922

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135630

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:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000685

AC:

AN:

1460848

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

726658

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:

0.0000349

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000630

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

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

Jun 28, 2023

The c.1184T>C (p.I395T) alteration is located in exon 11 (coding exon 9) of the ACSM2B gene. This alteration results from a T to C substitution at nucleotide position 1184, causing the isoleucine (I) at amino acid position 395 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

0.17

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.058

T;T;.;T;T;.

Eigen

Benign

0.069

Eigen_PC

Benign

-0.082

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.74

.;T;T;.;.;D

M_CAP

Benign

0.0069

MetaRNN

Pathogenic

0.90

D;D;D;D;D;D

MetaSVM

Benign

-0.85

MutationAssessor

Uncertain

2.8

M;M;.;M;M;.

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.45

PROVEAN

Uncertain

-3.7

D;.;D;D;D;.

REVEL

Uncertain

0.29

Sift

Uncertain

0.0080

D;.;D;D;D;.

Sift4G

Benign

0.14

T;T;T;T;T;D

Polyphen

0.78

P;P;.;P;P;.

Vest4

0.69

MutPred

0.79

Gain of disorder (P = 0.0248);Gain of disorder (P = 0.0248);.;Gain of disorder (P = 0.0248);Gain of disorder (P = 0.0248);.;

MVP

0.64

MPC

0.83

ClinPred

0.92

GERP RS

3.4

Varity_R

0.31

gMVP

0.58

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