Variant 10-95211922-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_207321.3(ACSM6):c.800G>A(p.Gly267Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ACSM6
NM_207321.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.82

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ACSM6	NM_207321.3 linkuse as main transcript	c.800G>A	p.Gly267Asp	missense_variant	6/11	ENST00000394005.4	NP_997204.2
LOC107984257	XR_007062253.1 linkuse as main transcript	n.347+13626C>T		intron_variant, non_coding_transcript_variant
ACSM6	XM_047424638.1 linkuse as main transcript	c.800G>A	p.Gly267Asp	missense_variant	6/10		XP_047280594.1
ACSM6	XM_047424639.1 linkuse as main transcript	c.800G>A	p.Gly267Asp	missense_variant	5/9		XP_047280595.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACSM6	ENST00000394005.4 linkuse as main transcript	c.800G>A	p.Gly267Asp	missense_variant	6/11	5	NM_207321.3	ENSP00000377573	P1	Q6P461-1
ACSM6	ENST00000404473.6 linkuse as main transcript	c.*623G>A		3_prime_UTR_variant, NMD_transcript_variant	6/10	1		ENSP00000384922
ACSM6	ENST00000327739.7 linkuse as main transcript	c.*364G>A		3_prime_UTR_variant, NMD_transcript_variant	6/9	2		ENSP00000328491

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1461230

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726864

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:

0.00

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.800G>A (p.G267D) alteration is located in exon 6 (coding exon 5) of the ACSM6 gene. This alteration results from a G to A substitution at nucleotide position 800, causing the glycine (G) at amino acid position 267 to be replaced by an aspartic acid (D). 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

0.12

BayesDel_addAF

Benign

-0.0091

BayesDel_noAF

Benign

-0.25

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.016

T;T

Eigen

Benign

-0.39

Eigen_PC

Benign

-0.57

FATHMM_MKL

Benign

0.040

LIST_S2

Benign

0.36

T;.

M_CAP

Benign

0.0053

MetaRNN

Uncertain

0.50

D;D

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

N;N

MutationTaster

Benign

1.0

N;N;N

PROVEAN

Benign

-0.71

N;N

REVEL

Benign

0.25

Sift

Uncertain

0.0010

D;D

Sift4G

Uncertain

0.0050

D;D

Polyphen

0.95

P;P

Vest4

0.47

MutPred

0.78

Gain of catalytic residue at G267 (P = 0.1297);Gain of catalytic residue at G267 (P = 0.1297);

MVP

0.24

MPC

0.067

ClinPred

0.50

GERP RS

0.81

Varity_R

0.57

gMVP

0.82

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