Variant 10-95202016-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_207321.3(ACSM6):c.224G>C(p.Trp75Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000214 in 1,399,464 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ACSM6
NM_207321.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.50

Variant links:

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]

ACSM6 links:

LOC107984257 (HGNC:):

LOC107984257 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.886

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ACSM6	NM_207321.3 linkuse as main transcript	c.224G>C	p.Trp75Ser	missense_variant	3/11	ENST00000394005.4
LOC107984257	XR_007062253.1 linkuse as main transcript	n.347+23532C>G		intron_variant, non_coding_transcript_variant
ACSM6	XM_047424638.1 linkuse as main transcript	c.224G>C	p.Trp75Ser	missense_variant	3/10
ACSM6	XM_047424639.1 linkuse as main transcript	c.224G>C	p.Trp75Ser	missense_variant	2/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACSM6	ENST00000394005.4 linkuse as main transcript	c.224G>C	p.Trp75Ser	missense_variant	3/11	5	NM_207321.3	P1	Q6P461-1
ACSM6	ENST00000404473.6 linkuse as main transcript	c.*47G>C		3_prime_UTR_variant, NMD_transcript_variant	3/10	1
ACSM6	ENST00000327739.7 linkuse as main transcript	c.224G>C	p.Trp75Ser	missense_variant, NMD_transcript_variant	3/9	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000191

AC:

AN:

156702

Hom.:

AF XY:

0.0000241

AC XY:

AN XY:

82968

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000122

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000214

AC:

AN:

1399464

Hom.:

Cov.:

AF XY:

0.00000290

AC XY:

AN XY:

690238

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000840

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 09, 2021

The c.224G>C (p.W75S) alteration is located in exon 3 (coding exon 2) of the ACSM6 gene. This alteration results from a G to C substitution at nucleotide position 224, causing the tryptophan (W) at amino acid position 75 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.75

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.30

Cadd

Benign

Dann

Benign

0.97

DEOGEN2

Benign

0.077

T;T

Eigen

Benign

0.049

Eigen_PC

Benign

-0.17

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.37

T;.

M_CAP

Benign

0.0037

MetaRNN

Pathogenic

0.89

D;D

MetaSVM

Benign

-0.84

MutationAssessor

Uncertain

2.2

M;M

MutationTaster

Benign

0.99

D;N;N

PROVEAN

Pathogenic

-13

D;D

REVEL

Benign

0.23

Sift

Pathogenic

0.0

D;D

Sift4G

Uncertain

0.0070

D;D

Polyphen

1.0

D;D

Vest4

0.65

MutPred

0.73

Gain of disorder (P = 2e-04);Gain of disorder (P = 2e-04);

MVP

0.45

MPC

0.034

ClinPred

0.96

GERP RS

1.3

Varity_R

0.69

gMVP

0.50

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over