rs1004167462

Variant names:

• chr10-95194580-C-G
• rs1004167462
• NM_207321.3:c.95C>G

Your query was ambiguous. Multiple possible variants found:

• chr10-95194580-C-G
• chr10-95194580-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_207321.3(ACSM6):​c.95C>G​(p.Thr32Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000714 in 1,399,716 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T32I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: ACSM6 NM_207321.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.422
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.043183893).

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.95C>G	p.Thr32Ser	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.95C>G	p.Thr32Ser	missense	Exon 2 of 11	ENSP00000377573.3	Q6P461-1
	ACSM6	ENST00000404473.6	TSL:1	n.95C>G		non_coding_transcript_exon	Exon 1 of 10	ENSP00000384922.2	H7BYZ2
	ACSM6	ENST00000327739.7	TSL:2	n.95C>G		non_coding_transcript_exon	Exon 2 of 9	ENSP00000328491.3	H7BXS6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000631 AC: 1 AN: 158390 AF XY: 0.0000120

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000162

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.14e-7 AC: 1 AN: 1399716 Hom.: 0 Cov.: 41 AF XY: 0.00 AC XY: 0 AN XY: 690358

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 31596

American (AMR) AF: 0.00 AC: 0 AN: 35706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25182

East Asian (EAS) AF: 0.00 AC: 0 AN: 35738

South Asian (SAS) AF: 0.00 AC: 0 AN: 79230

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49436

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5702

European-Non Finnish (NFE) AF: 9.27e-7 AC: 1 AN: 1078988

Other (OTH) AF: 0.00 AC: 0 AN: 58138

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

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	0.084
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.10
DANN	Benign	0.45
DEOGEN2	Benign	0.015	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0060	N
LIST_S2	Benign	0.29	T
M_CAP	Benign	0.0010	T
MetaRNN	Benign	0.043	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.42
PROVEAN	Benign	-0.070	N
REVEL	Benign	0.0080
Sift	Benign	0.47	T
Sift4G	Benign	0.34	T
Polyphen		0.0060	B
Vest4		0.039
MutPred		0.30		Gain of disorder (P = 0.0426)
MVP		0.055
MPC		0.022
ClinPred		0.023	T
GERP RS		0.74
PromoterAI		0.0022	Neutral
Varity_R		0.041
gMVP		0.18
Mutation Taster		=98/2	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: rs1004167462; hg19: chr10-96954337;