Variant 16-20781708-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000289416.10(ACSM3):c.940A>T(p.Thr314Ser) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000137 in 1,458,884 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ACSM3
ENST00000289416.10 missense, splice_region

Scores

Splicing: ADA: 0.9111

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.74

Variant links:

Genes affected

ACSM3 (HGNC:10522): (acyl-CoA synthetase medium chain family member 3) Enables butyrate-CoA ligase activity. Predicted to be involved in acyl-CoA metabolic process and fatty acid biosynthetic process. Located in mitochondrion. Implicated in IgA glomerulonephritis. Biomarker of ulcerative colitis. [provided by Alliance of Genome Resources, Apr 2022]

ACSM3 links:

ERI2 (HGNC:30541): (ERI1 exoribonuclease family member 2) Predicted to enable 3'-5'-exoribonuclease activity. Predicted to be involved in exonucleolytic trimming to generate mature 3'-end of 5.8S rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA). [provided by Alliance of Genome Resources, Apr 2022]

ERI2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACSM3	NM_005622.4 linkuse as main transcript	c.940A>T	p.Thr314Ser	missense_variant, splice_region_variant	7/14	ENST00000289416.10	NP_005613.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACSM3	ENST00000289416.10 linkuse as main transcript	c.940A>T	p.Thr314Ser	missense_variant, splice_region_variant	7/14	1	NM_005622.4	ENSP00000289416	P1	Q53FZ2-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1458884

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

725984

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:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

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

May 20, 2024

The c.940A>T (p.T314S) alteration is located in exon 7 (coding exon 6) of the ACSM3 gene. This alteration results from a A to T substitution at nucleotide position 940, causing the threonine (T) at amino acid position 314 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

Benign

0.18

BayesDel_addAF

Uncertain

0.067

BayesDel_noAF

Benign

-0.14

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.20

T;.

Eigen

Uncertain

0.64

Eigen_PC

Uncertain

0.64

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.69

T;T

M_CAP

Benign

0.012

MetaRNN

Uncertain

0.44

T;T

MetaSVM

Benign

-0.70

MutationAssessor

Pathogenic

3.1

M;M

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.50

PROVEAN

Uncertain

-3.1

D;D

REVEL

Benign

0.16

Sift

Benign

0.048

D;D

Sift4G

Benign

0.18

T;T

Polyphen

0.88

P;P

Vest4

0.29

MutPred

0.58

Gain of disorder (P = 0.0652);Gain of disorder (P = 0.0652);

MVP

0.74

MPC

0.17

ClinPred

0.97

GERP RS

5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.50

gMVP

0.33

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.91

dbscSNV1_RF

Pathogenic

0.77

SpliceAI score (max)

0.27

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.27

Position offset: 0

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over