rs591157

Variant names:

• chr10-95194541-A-G
• rs591157
• NM_207321.3:c.56A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_207321.3(ACSM6):​c.56A>G​(p.Glu19Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.532 in 1,551,332 control chromosomes in the GnomAD database, including 227,497 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.51 (20597 hom., cov: 32)
  • Exomes 𝑓: 0.53 (206900 hom.)
• Consequence: ACSM6 NM_207321.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.314
• Publications: 26 publications found

Genes affected

ACSM6 (HGNC:31665): (acyl-CoA synthetase medium chain family member 6) Predicted to enable fatty acid ligase activity and fatty-acyl-CoA synthase activity. Predicted to be involved in acyl-CoA metabolic process and fatty acid biosynthetic process. Predicted to be active in mitochondrial matrix. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000234026 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.7157197E-4).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.559 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_207321.3. 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
	ACSM6	NM_207321.3	MANE Select	c.56A>G	p.Glu19Gly	missense	Exon 2 of 11	NP_997204.2	Q6P461-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACSM6	ENST00000394005.4	TSL:5 MANE Select	c.56A>G	p.Glu19Gly	missense	Exon 2 of 11	ENSP00000377573.3	Q6P461-1
	ACSM6	ENST00000404473.6	TSL:1	n.56A>G		non_coding_transcript_exon	Exon 1 of 10	ENSP00000384922.2	H7BYZ2
	ACSM6	ENST00000327739.7	TSL:2	n.56A>G		non_coding_transcript_exon	Exon 2 of 9	ENSP00000328491.3	H7BXS6

Frequencies

GnomAD3 genomes AF: 0.510 AC: 77387 AN: 151862 Hom.: 20582 Cov.: 32

Gnomad AFR AF: 0.490

Gnomad AMI AF: 0.654

Gnomad AMR AF: 0.451

Gnomad ASJ AF: 0.572

Gnomad EAS AF: 0.0455

Gnomad SAS AF: 0.461

Gnomad FIN AF: 0.533

Gnomad MID AF: 0.655

Gnomad NFE AF: 0.563

Gnomad OTH AF: 0.542

GnomAD2 exomes AF: 0.472 AC: 74284 AN: 157376 AF XY: 0.480

Gnomad AFR exome AF: 0.485

Gnomad AMR exome AF: 0.327

Gnomad ASJ exome AF: 0.584

Gnomad EAS exome AF: 0.0430

Gnomad FIN exome AF: 0.546

Gnomad NFE exome AF: 0.566

Gnomad OTH exome AF: 0.528

GnomAD4 exome AF: 0.535 AC: 748318 AN: 1399352 Hom.: 206900 Cov.: 55 AF XY: 0.534 AC XY: 368640 AN XY: 690208

African (AFR) AF: 0.485 AC: 15323 AN: 31586

American (AMR) AF: 0.346 AC: 12363 AN: 35704

Ashkenazi Jewish (ASJ) AF: 0.578 AC: 14550 AN: 25178

East Asian (EAS) AF: 0.0351 AC: 1254 AN: 35738

South Asian (SAS) AF: 0.472 AC: 37412 AN: 79226

European-Finnish (FIN) AF: 0.538 AC: 26538 AN: 49336

Middle Eastern (MID) AF: 0.622 AC: 3544 AN: 5696

European-Non Finnish (NFE) AF: 0.563 AC: 606986 AN: 1078838

Other (OTH) AF: 0.523 AC: 30348 AN: 58050

GnomAD4 genome AF: 0.510 AC: 77434 AN: 151980 Hom.: 20597 Cov.: 32 AF XY: 0.505 AC XY: 37511 AN XY: 74282

African (AFR) AF: 0.490 AC: 20304 AN: 41442

American (AMR) AF: 0.450 AC: 6868 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.572 AC: 1986 AN: 3470

East Asian (EAS) AF: 0.0455 AC: 235 AN: 5170

South Asian (SAS) AF: 0.461 AC: 2226 AN: 4824

European-Finnish (FIN) AF: 0.533 AC: 5620 AN: 10550

Middle Eastern (MID) AF: 0.660 AC: 194 AN: 294

European-Non Finnish (NFE) AF: 0.563 AC: 38279 AN: 67958

Other (OTH) AF: 0.536 AC: 1127 AN: 2102

Alfa AF: 0.542 Hom.: 105535

Bravo AF: 0.501

TwinsUK AF: 0.577 AC: 2141

ALSPAC AF: 0.555 AC: 2138

ESP6500AA AF: 0.496 AC: 686

ESP6500EA AF: 0.564 AC: 1796

ExAC AF: 0.491 AC: 12190

Asia WGS AF: 0.282 AC: 982 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.80	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	2.6
DANN	Benign	0.89
DEOGEN2	Benign	0.016	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.000050	N
LIST_S2	Benign	0.21	T
MetaRNN	Benign	0.00017	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.31
PROVEAN	Benign	0.26	N
REVEL	Benign	0.023
Sift	Benign	0.26	T
Sift4G	Benign	0.41	T
Polyphen		0.0	B
Vest4		0.041
MPC		0.024
ClinPred		0.0068	T
GERP RS		1.3
PromoterAI		0.00070	Neutral
Varity_R		0.029
gMVP		0.42
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: rs591157; hg19: chr10-96954298; COSMIC: COSV58977536;