16-20552222-T-G

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001105069.2(ACSM2B):c.816A>C(p.Ser272=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0112 in 1,613,814 control chromosomes in the GnomAD database, including 162 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0083 (13 hom., cov: 32)
  • Exomes 𝑓: 0.011 (149 hom.)
• Consequence: ACSM2B NM_001105069.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.53

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]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 16-20552222-T-G is Benign according to our data. Variant chr16-20552222-T-G is described in ClinVar as [Benign]. Clinvar id is 773578.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.53 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACSM2B	NM_001105069.2	c.816A>C	p.Ser272=	synonymous_variant	6/14	ENST00000329697.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACSM2B	ENST00000329697.10	c.816A>C	p.Ser272=	synonymous_variant	6/14	1	NM_001105069.2	P1

Frequencies

GnomAD3 genomes AF: 0.00830 AC: 1262 AN: 152110 Hom.: 13 Cov.: 32

Gnomad AFR AF: 0.00241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00465

Gnomad ASJ AF: 0.00260

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00684

Gnomad FIN AF: 0.0139

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0130

Gnomad OTH AF: 0.00814

GnomAD3 exomes AF: 0.00826 AC: 2077 AN: 251334 Hom.: 14 AF XY: 0.00852 AC XY: 1157 AN XY: 135848

Gnomad AFR exome AF: 0.00154

Gnomad AMR exome AF: 0.00255

Gnomad ASJ exome AF: 0.00159

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00644

Gnomad FIN exome AF: 0.0128

Gnomad NFE exome AF: 0.0122

Gnomad OTH exome AF: 0.0135

GnomAD4 exome AF: 0.0115 AC: 16758 AN: 1461586 Hom.: 149 Cov.: 31 AF XY: 0.0112 AC XY: 8173 AN XY: 727108

Gnomad4 AFR exome AF: 0.00191

Gnomad4 AMR exome AF: 0.00291

Gnomad4 ASJ exome AF: 0.00176

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00720

Gnomad4 FIN exome AF: 0.0147

Gnomad4 NFE exome AF: 0.0130

Gnomad4 OTH exome AF: 0.0113

GnomAD4 genome AF: 0.00828 AC: 1261 AN: 152228 Hom.: 13 Cov.: 32 AF XY: 0.00830 AC XY: 618 AN XY: 74426

Gnomad4 AFR AF: 0.00241

Gnomad4 AMR AF: 0.00464

Gnomad4 ASJ AF: 0.00260

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00685

Gnomad4 FIN AF: 0.0139

Gnomad4 NFE AF: 0.0130

Gnomad4 OTH AF: 0.00806

Alfa AF: 0.0103 Hom.: 7

Bravo AF: 0.00680

Asia WGS AF: 0.00346 AC: 12 AN: 3478

EpiCase AF: 0.0111

EpiControl AF: 0.0120

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Aug 18, 2017

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.074
Dann	Benign	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

Other links and lift over

dbSNP: rs35623745; hg19: chr16-20563544;