chr16-20553871-A-T

Variant summary

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

The NM_001105069.2(ACSM2B):​c.646T>A​(p.Ser216Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,190 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

ACSM2B
NM_001105069.2 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.285
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]

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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=0.09272322).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ACSM2BNM_001105069.2 linkuse as main transcriptc.646T>A p.Ser216Thr missense_variant 5/14 ENST00000329697.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ACSM2BENST00000329697.10 linkuse as main transcriptc.646T>A p.Ser216Thr missense_variant 5/141 NM_001105069.2 P1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152190
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
Cov.:
31
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152190
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74360
show subpopulations
Gnomad4 AFR
AF:
0.0000241
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:
0.00
Gnomad4 OTH
AF:
0.00

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, 2021The c.646T>A (p.S216T) alteration is located in exon 6 (coding exon 4) of the ACSM2B gene. This alteration results from a T to A substitution at nucleotide position 646, causing the serine (S) at amino acid position 216 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
0.10
BayesDel_addAF
Benign
-0.22
T
BayesDel_noAF
Benign
-0.56
CADD
Benign
5.5
DANN
Benign
0.62
DEOGEN2
Benign
0.0035
T;T;.;T;T;.
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.040
N
LIST_S2
Benign
0.81
.;T;T;.;.;T
M_CAP
Benign
0.0023
T
MetaRNN
Benign
0.093
T;T;T;T;T;T
MetaSVM
Benign
-0.93
T
MutationAssessor
Benign
2.0
M;M;.;M;M;.
MutationTaster
Benign
1.0
N;N;N;N
PrimateAI
Benign
0.30
T
PROVEAN
Benign
-0.050
N;.;N;N;N;N
REVEL
Benign
0.041
Sift
Benign
0.055
T;.;D;T;T;T
Sift4G
Benign
0.10
T;T;T;T;T;T
Polyphen
0.062
B;B;.;B;B;.
Vest4
0.17
MutPred
0.55
Loss of disorder (P = 0.0804);Loss of disorder (P = 0.0804);.;Loss of disorder (P = 0.0804);Loss of disorder (P = 0.0804);.;
MVP
0.18
MPC
0.96
ClinPred
0.10
T
GERP RS
0.18
Varity_R
0.11
gMVP
0.44

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.

Other links and lift over

dbSNP: rs2015390235; hg19: chr16-20565193; API