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16-20636754-G-T

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Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001318890.3(ACSM1):​c.1284C>A​(p.Leu428=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00512 in 1,613,998 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0034 ( 1 hom., cov: 32)
Exomes 𝑓: 0.0053 ( 26 hom. )

Consequence

ACSM1
NM_001318890.3 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0380
Variant links:
Genes affected
ACSM1 (HGNC:18049): (acyl-CoA synthetase medium chain family member 1) Enables CoA-ligase activity. Predicted to be involved in acyl-CoA metabolic process and fatty acid biosynthetic process. Located in mitochondrial matrix. [provided by Alliance of Genome Resources, Apr 2022]
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.61).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 16-20636754-G-T is Benign according to our data. Variant chr16-20636754-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 2646284.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.038 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAdExome4 at 26 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ACSM1NM_001318890.3 linkuse as main transcriptc.1284C>A p.Leu428= synonymous_variant 10/14 ENST00000520010.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ACSM1ENST00000520010.6 linkuse as main transcriptc.1284C>A p.Leu428= synonymous_variant 10/141 NM_001318890.3 P1Q08AH1-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00345
AC:
525
AN:
152212
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00142
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00484
Gnomad ASJ
AF:
0.000288
Gnomad EAS
AF:
0.000192
Gnomad SAS
AF:
0.00145
Gnomad FIN
AF:
0.00104
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00533
Gnomad OTH
AF:
0.00430
GnomAD3 exomes
AF:
0.00306
AC:
769
AN:
251170
Hom.:
3
AF XY:
0.00312
AC XY:
423
AN XY:
135720
show subpopulations
Gnomad AFR exome
AF:
0.000984
Gnomad AMR exome
AF:
0.00266
Gnomad ASJ exome
AF:
0.000397
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00206
Gnomad FIN exome
AF:
0.00143
Gnomad NFE exome
AF:
0.00473
Gnomad OTH exome
AF:
0.00425
GnomAD4 exome
AF:
0.00530
AC:
7745
AN:
1461668
Hom.:
26
Cov.:
30
AF XY:
0.00516
AC XY:
3750
AN XY:
727138
show subpopulations
Gnomad4 AFR exome
AF:
0.000807
Gnomad4 AMR exome
AF:
0.00257
Gnomad4 ASJ exome
AF:
0.000574
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00194
Gnomad4 FIN exome
AF:
0.00180
Gnomad4 NFE exome
AF:
0.00628
Gnomad4 OTH exome
AF:
0.00560
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00345
AC:
525
AN:
152330
Hom.:
1
Cov.:
32
AF XY:
0.00318
AC XY:
237
AN XY:
74486
show subpopulations
Gnomad4 AFR
AF:
0.00142
Gnomad4 AMR
AF:
0.00484
Gnomad4 ASJ
AF:
0.000288
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00145
Gnomad4 FIN
AF:
0.00104
Gnomad4 NFE
AF:
0.00534
Gnomad4 OTH
AF:
0.00425
Alfa
AF:
0.00295
Hom.:
0
Bravo
AF:
0.00367
Asia WGS
AF:
0.00115
AC:
4
AN:
3478
EpiCase
AF:
0.00464
EpiControl
AF:
0.00522

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenMar 01, 2022ACSM1: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.61
CADD
Benign
1.9
DANN
Benign
0.54

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.19
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: rs61739414; hg19: chr16-20648076; API