rs591157

Positions:

• chr10-95194541-A-G

Variant summary

Our verdict is Benign. Variant got -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. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• 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

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]

LOC107984257 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACSM6	NM_207321.3	c.56A>G	p.Glu19Gly	missense_variant	2/11	ENST00000394005.4	NP_997204.2
LOC107984257	XR_007062253.1	n.348-21354T>C		intron_variant, non_coding_transcript_variant
ACSM6	XM_047424638.1	c.56A>G	p.Glu19Gly	missense_variant	2/10		XP_047280594.1
ACSM6	XM_047424639.1	c.56A>G	p.Glu19Gly	missense_variant	1/9		XP_047280595.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACSM6	ENST00000394005.4	c.56A>G	p.Glu19Gly	missense_variant	2/11	5	NM_207321.3	ENSP00000377573	P1
ACSM6	ENST00000404473.6	c.56A>G	p.Glu19Gly	missense_variant, NMD_transcript_variant	1/10	1		ENSP00000384922
ACSM6	ENST00000327739.7	c.56A>G	p.Glu19Gly	missense_variant, NMD_transcript_variant	2/9	2		ENSP00000328491

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

GnomAD3 exomes AF: 0.472 AC: 74284 AN: 157376 Hom.: 19370 AF XY: 0.480 AC XY: 39905 AN XY: 83214

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 SAS exome AF: 0.470

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

Gnomad4 AFR exome AF: 0.485

Gnomad4 AMR exome AF: 0.346

Gnomad4 ASJ exome AF: 0.578

Gnomad4 EAS exome AF: 0.0351

Gnomad4 SAS exome AF: 0.472

Gnomad4 FIN exome AF: 0.538

Gnomad4 NFE exome AF: 0.563

Gnomad4 OTH exome AF: 0.523

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

Gnomad4 AFR AF: 0.490

Gnomad4 AMR AF: 0.450

Gnomad4 ASJ AF: 0.572

Gnomad4 EAS AF: 0.0455

Gnomad4 SAS AF: 0.461

Gnomad4 FIN AF: 0.533

Gnomad4 NFE AF: 0.563

Gnomad4 OTH AF: 0.536

Alfa AF: 0.551 Hom.: 52391

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 v4.3

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;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;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.0	N;N
MutationTaster	Benign	1.0	P;P;P
PROVEAN	Benign	0.26	N;N
REVEL	Benign	0.023
Sift	Benign	0.26	T;T
Sift4G	Benign	0.41	T;T
Polyphen		0.0	B;B
Vest4		0.041
MPC		0.024
ClinPred		0.0068	T
GERP RS		1.3
Varity_R		0.029
gMVP		0.42

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: rs591157; hg19: chr10-96954298; COSMIC: COSV58977536;