16-20548404-C-T

Variant names:

• chr16-20548404-C-T
• rs138313532
• NM_001105069.2:c.964G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001105069.2(ACSM2B):​c.964G>A​(p.Asp322Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00872 in 1,613,598 control chromosomes in the GnomAD database, including 72 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D322Y) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0072 (6 hom., cov: 32)
  • Exomes 𝑓: 0.0089 (66 hom.)
• Consequence: ACSM2B NM_001105069.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.27
• Publications: 9 publications found

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

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.00947082).
• BS2: High Homozygotes in GnomAd4 at 6 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001105069.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACSM2B	NM_001105069.2	MANE Select	c.964G>A	p.Asp322Asn	missense	Exon 7 of 14	NP_001098539.1	Q68CK6
	ACSM2B	NM_182617.4		c.964G>A	p.Asp322Asn	missense	Exon 8 of 15	NP_872423.3
	ACSM2B	NM_001410902.1		c.727G>A	p.Asp243Asn	missense	Exon 6 of 13	NP_001397831.1	H3BTX9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACSM2B	ENST00000329697.10	TSL:1 MANE Select	c.964G>A	p.Asp322Asn	missense	Exon 7 of 14	ENSP00000327453.6	Q68CK6
	ACSM2B	ENST00000414188.6	TSL:1	c.964G>A	p.Asp322Asn	missense	Exon 6 of 13	ENSP00000390378.3	Q68CK6
	ACSM2B	ENST00000567001.5	TSL:1	c.964G>A	p.Asp322Asn	missense	Exon 8 of 15	ENSP00000456378.1	Q68CK6

Frequencies

GnomAD3 genomes AF: 0.00725 AC: 1102 AN: 152076 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.00213

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0116

Gnomad ASJ AF: 0.00490

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00311

Gnomad FIN AF: 0.00330

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0108

Gnomad OTH AF: 0.0100

GnomAD2 exomes AF: 0.00709 AC: 1779 AN: 251020 AF XY: 0.00747

Gnomad AFR exome AF: 0.00191

Gnomad AMR exome AF: 0.00622

Gnomad ASJ exome AF: 0.00506

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00457

Gnomad NFE exome AF: 0.0106

Gnomad OTH exome AF: 0.00833

GnomAD4 exome AF: 0.00887 AC: 12965 AN: 1461404 Hom.: 66 Cov.: 31 AF XY: 0.00897 AC XY: 6525 AN XY: 727038

African (AFR) AF: 0.00192 AC: 64 AN: 33408

American (AMR) AF: 0.00622 AC: 278 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00517 AC: 135 AN: 26128

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39700

South Asian (SAS) AF: 0.00427 AC: 368 AN: 86228

European-Finnish (FIN) AF: 0.00417 AC: 223 AN: 53416

Middle Eastern (MID) AF: 0.00851 AC: 49 AN: 5760

European-Non Finnish (NFE) AF: 0.0102 AC: 11336 AN: 1111694

Other (OTH) AF: 0.00845 AC: 510 AN: 60362

GnomAD4 genome AF: 0.00723 AC: 1100 AN: 152194 Hom.: 6 Cov.: 32 AF XY: 0.00679 AC XY: 505 AN XY: 74422

African (AFR) AF: 0.00212 AC: 88 AN: 41496

American (AMR) AF: 0.0116 AC: 177 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00490 AC: 17 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5174

South Asian (SAS) AF: 0.00311 AC: 15 AN: 4818

European-Finnish (FIN) AF: 0.00330 AC: 35 AN: 10614

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0108 AC: 736 AN: 68010

Other (OTH) AF: 0.00993 AC: 21 AN: 2114

Alfa AF: 0.00830 Hom.: 1

Bravo AF: 0.00746

TwinsUK AF: 0.00890 AC: 33

ALSPAC AF: 0.00960 AC: 37

ESP6500AA AF: 0.00250 AC: 11

ESP6500EA AF: 0.0109 AC: 94

ExAC AF: 0.00688 AC: 835

EpiCase AF: 0.0125

EpiControl AF: 0.0119

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.049	T
Eigen	Benign	-0.098
Eigen_PC	Benign	-0.018
FATHMM_MKL	Benign	0.73	D
LIST_S2	Uncertain	0.89	D
MetaRNN	Benign	0.0095	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		2.3
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.11
Sift	Benign	0.11	T
Sift4G	Benign	0.10	T
Polyphen		0.066	B
Vest4		0.30
MVP		0.50
MPC		0.99
ClinPred		0.018	T
GERP RS		3.6
Varity_R		0.15
gMVP		0.34
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs138313532; hg19: chr16-20559726; COSMIC: COSV61657318; COSMIC: COSV61657318;