10-95214938-A-G

Variant names:

• chr10-95214938-A-G
• rs1466596617
• NM_207321.3:c.1082A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_207321.3(ACSM6):​c.1082A>G​(p.Lys361Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 152,190 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.000013 (0 hom., cov: 32)
• Consequence: ACSM6 NM_207321.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.34
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21785414).

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.1082A>G	p.Lys361Arg	missense	Exon 8 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.1082A>G	p.Lys361Arg	missense	Exon 8 of 11	ENSP00000377573.3	Q6P461-1
	ACSM6	ENST00000404473.6	TSL:1	n.*905A>G		non_coding_transcript_exon	Exon 8 of 10	ENSP00000384922.2	H7BYZ2
	ACSM6	ENST00000404473.6	TSL:1	n.*905A>G		3_prime_UTR	Exon 8 of 10	ENSP00000384922.2	H7BYZ2

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152190 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152190 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74346

African (AFR) AF: 0.0000483 AC: 2 AN: 41440

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0091	T
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.65
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.0027	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.90	L
PhyloP100		2.3
PROVEAN	Benign	-0.16	N
REVEL	Benign	0.14
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.65	P
Vest4		0.18
MutPred		0.78		Loss of methylation at K361 (P = 0.0497)
MVP		0.12
MPC		0.067
ClinPred		0.59	D
GERP RS		-0.55
Varity_R		0.23
gMVP		0.26
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.19		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: rs1466596617; hg19: chr10-96974695;