NM_001105069.2:c.913A>G

Variant names:

• chr16-20548455-T-C
• rs80135299
• NM_001105069.2:c.913A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001105069.2(ACSM2B):​c.913A>G​(p.Ile305Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00748 in 1,612,000 control chromosomes in the GnomAD database, including 1,009 homozygotes. 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 Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.045 (522 hom., cov: 32)
  • Exomes 𝑓: 0.0036 (487 hom.)
• Consequence: ACSM2B NM_001105069.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.12
• Publications: 3 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0019419491).
• BP6: Variant 16-20548455-T-C is Benign according to our data. Variant chr16-20548455-T-C is described in ClinVar as Benign. ClinVar VariationId is 776988.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.153 is higher than 0.05.

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.913A>G	p.Ile305Val	missense	Exon 7 of 14	NP_001098539.1	Q68CK6
	ACSM2B	NM_182617.4		c.913A>G	p.Ile305Val	missense	Exon 8 of 15	NP_872423.3
	ACSM2B	NM_001410902.1		c.676A>G	p.Ile226Val	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.913A>G	p.Ile305Val	missense	Exon 7 of 14	ENSP00000327453.6	Q68CK6
	ACSM2B	ENST00000414188.6	TSL:1	c.913A>G	p.Ile305Val	missense	Exon 6 of 13	ENSP00000390378.3	Q68CK6
	ACSM2B	ENST00000567001.5	TSL:1	c.913A>G	p.Ile305Val	missense	Exon 8 of 15	ENSP00000456378.1	Q68CK6

Frequencies

GnomAD3 genomes AF: 0.0444 AC: 6744 AN: 151914 Hom.: 519 Cov.: 32

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0164

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000397

Gnomad OTH AF: 0.0244

GnomAD2 exomes AF: 0.00873 AC: 2190 AN: 250718 AF XY: 0.00659

Gnomad AFR exome AF: 0.120

Gnomad AMR exome AF: 0.00611

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000273

Gnomad OTH exome AF: 0.00408

GnomAD4 exome AF: 0.00361 AC: 5270 AN: 1459968 Hom.: 487 Cov.: 31 AF XY: 0.00311 AC XY: 2257 AN XY: 726414

African (AFR) AF: 0.130 AC: 4190 AN: 32294

American (AMR) AF: 0.00746 AC: 333 AN: 44660

Ashkenazi Jewish (ASJ) AF: 0.0000766 AC: 2 AN: 26116

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.000325 AC: 28 AN: 86226

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00452 AC: 26 AN: 5754

European-Non Finnish (NFE) AF: 0.000147 AC: 163 AN: 1111574

Other (OTH) AF: 0.00877 AC: 528 AN: 60230

GnomAD4 genome AF: 0.0446 AC: 6780 AN: 152032 Hom.: 522 Cov.: 32 AF XY: 0.0443 AC XY: 3290 AN XY: 74344

African (AFR) AF: 0.156 AC: 6449 AN: 41308

American (AMR) AF: 0.0163 AC: 250 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000397 AC: 27 AN: 68018

Other (OTH) AF: 0.0241 AC: 51 AN: 2114

Alfa AF: 0.0419 Hom.: 214

Bravo AF: 0.0510

ESP6500AA AF: 0.0971 AC: 427

ESP6500EA AF: 0.000698 AC: 6

ExAC AF: 0.00972 AC: 1180

EpiCase AF: 0.000764

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	8.4
DANN	Benign	0.41
DEOGEN2	Benign	0.0095	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.51	T
MetaRNN	Benign	0.0019	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.91	L
PhyloP100		1.1
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.74	N
REVEL	Benign	0.058
Sift	Benign	0.15	T
Sift4G	Benign	0.24	T
Polyphen		0.033	B
Vest4		0.23
MVP		0.30
MPC		0.89
ClinPred		0.0042	T
GERP RS		-0.040
Varity_R		0.058
gMVP		0.40
Mutation Taster		=100/0	polymorphism (auto)

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: rs80135299; hg19: chr16-20559777;