Variant 16-20418116-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The ENST00000331849.8(ACSM5):c.262A>G(p.Ile88Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000558 in 1,613,684 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

ACSM5
ENST00000331849.8 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.84

Variant links:

Genes affected

ACSM5 (HGNC:26060): (acyl-CoA synthetase medium chain family member 5) Predicted to enable fatty acid ligase activity and fatty-acyl-CoA synthase activity. Predicted to be involved in acyl-CoA metabolic process and fatty acid biosynthetic process. Predicted to be active in mitochondrial matrix. [provided by Alliance of Genome Resources, Apr 2022]

ACSM5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.035021037).

BP6

Variant 16-20418116-A-G is Benign according to our data. Variant chr16-20418116-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3140719.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACSM5	NM_017888.3 linkuse as main transcript	c.262A>G	p.Ile88Val	missense_variant	3/14	ENST00000331849.8	NP_060358.2	Q6NUN0-1
ACSM5	NM_001324372.2 linkuse as main transcript	c.262A>G	p.Ile88Val	missense_variant	3/14		NP_001311301.1
ACSM5	NM_001324371.2 linkuse as main transcript	c.262A>G	p.Ile88Val	missense_variant	3/14		NP_001311300.1	Q6NUN0-1
ACSM5	NM_001324373.2 linkuse as main transcript	c.262A>G	p.Ile88Val	missense_variant	3/4		NP_001311302.1	Q6NUN0-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACSM5	ENST00000331849.8 linkuse as main transcript	c.262A>G	p.Ile88Val	missense_variant	3/14	1	NM_017888.3	ENSP00000327916.4		Q6NUN0-1
ACSM5	ENST00000575584.5 linkuse as main transcript	c.262A>G	p.Ile88Val	missense_variant	3/4	1		ENSP00000460112.1		Q6NUN0-2

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152090

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000966

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

AF:

0.00000342

AC:

AN:

1461594

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727092

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

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:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152090

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74296

show subpopulations

Gnomad4 AFR

AF:

0.0000966

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

Alfa

AF:

0.0000986

Hom.:

Bravo

AF:

0.0000264

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 26, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.75

CADD

Benign

3.8

DANN

Benign

0.27

DEOGEN2

Benign

0.0049

.;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.078

LIST_S2

Benign

0.45

T;T

M_CAP

Benign

0.0030

MetaRNN

Benign

0.035

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-1.0

N;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.31

PROVEAN

Benign

0.48

.;N

REVEL

Benign

0.060

Sift

Benign

1.0

.;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

.;B

Vest4

0.11

MutPred

0.26

Gain of methylation at K89 (P = 0.0614);Gain of methylation at K89 (P = 0.0614);

MVP

0.28

MPC

0.12

ClinPred

0.036

GERP RS

-1.0

Varity_R

0.028

gMVP

0.33

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