Variant 10-95194544-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_207321.3(ACSM6):c.59C>G(p.Ala20Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000214 in 1,399,518 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

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: -0.0570

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10305518).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ACSM6	NM_207321.3 linkuse as main transcript	c.59C>G	p.Ala20Gly	missense_variant	2/11	ENST00000394005.4
LOC107984257	XR_007062253.1 linkuse as main transcript	n.348-21357G>C		intron_variant, non_coding_transcript_variant
ACSM6	XM_047424638.1 linkuse as main transcript	c.59C>G	p.Ala20Gly	missense_variant	2/10
ACSM6	XM_047424639.1 linkuse as main transcript	c.59C>G	p.Ala20Gly	missense_variant	1/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACSM6	ENST00000394005.4 linkuse as main transcript	c.59C>G	p.Ala20Gly	missense_variant	2/11	5	NM_207321.3	P1	Q6P461-1
ACSM6	ENST00000404473.6 linkuse as main transcript	c.59C>G	p.Ala20Gly	missense_variant, NMD_transcript_variant	1/10	1
ACSM6	ENST00000327739.7 linkuse as main transcript	c.59C>G	p.Ala20Gly	missense_variant, NMD_transcript_variant	2/9	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000127

AC:

AN:

157478

Hom.:

AF XY:

0.0000120

AC XY:

AN XY:

83234

show subpopulations

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000327

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000214

AC:

AN:

1399518

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

690296

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00000278

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

May 25, 2022

The c.59C>G (p.A20G) alteration is located in exon 2 (coding exon 1) of the ACSM6 gene. This alteration results from a C to G substitution at nucleotide position 59, causing the alanine (A) at amino acid position 20 to be replaced by a glycine (G). 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

Benign

0.078

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.66

Cadd

Benign

1.9

Dann

Benign

0.61

DEOGEN2

Benign

0.026

T;T

Eigen

Benign

-0.94

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.0078

LIST_S2

Benign

0.39

T;.

M_CAP

Benign

0.0015

MetaRNN

Benign

0.10

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.0

N;N

MutationTaster

Benign

1.0

N;N;N

PROVEAN

Benign

-0.76

N;N

REVEL

Benign

0.15

Sift

Benign

0.42

T;T

Sift4G

Benign

0.33

T;T

Polyphen

0.90

P;P

Vest4

0.26

MutPred

0.55

Loss of stability (P = 0.1122);Loss of stability (P = 0.1122);

MVP

0.040

MPC

0.024

ClinPred

0.078

GERP RS

-0.83

Varity_R

0.038

gMVP

0.26

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

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