Variant 10-95210672-T-C 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.634T>C(p.Tyr212His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,586 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: 32)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

ACSM6
NM_207321.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.82

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12154096).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ACSM6	NM_207321.3 linkuse as main transcript	c.634T>C	p.Tyr212His	missense_variant	5/11	ENST00000394005.4
LOC107984257	XR_007062253.1 linkuse as main transcript	n.347+14876A>G		intron_variant, non_coding_transcript_variant
ACSM6	XM_047424638.1 linkuse as main transcript	c.634T>C	p.Tyr212His	missense_variant	5/10
ACSM6	XM_047424639.1 linkuse as main transcript	c.634T>C	p.Tyr212His	missense_variant	4/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACSM6	ENST00000394005.4 linkuse as main transcript	c.634T>C	p.Tyr212His	missense_variant	5/11	5	NM_207321.3	P1	Q6P461-1
ACSM6	ENST00000404473.6 linkuse as main transcript	c.*457T>C		3_prime_UTR_variant, NMD_transcript_variant	5/10	1
ACSM6	ENST00000327739.7 linkuse as main transcript	c.*198T>C		3_prime_UTR_variant, NMD_transcript_variant	5/9	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000279

AC:

AN:

250936

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135596

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000203

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:

0.00000547

AC:

AN:

1461586

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727088

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000179

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:

0.0000227

ExAC

AF:

0.0000165

AC:

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

Jan 22, 2024

The c.634T>C (p.Y212H) alteration is located in exon 5 (coding exon 4) of the ACSM6 gene. This alteration results from a T to C substitution at nucleotide position 634, causing the tyrosine (Y) at amino acid position 212 to be replaced by a histidine (H). 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

0.10

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.67

Cadd

Benign

Dann

Benign

0.96

DEOGEN2

Benign

0.014

T;T

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.57

FATHMM_MKL

Benign

0.38

LIST_S2

Benign

0.29

T;.

M_CAP

Benign

0.0041

MetaRNN

Benign

0.12

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.84

L;L

MutationTaster

Benign

1.0

N;N;N

PROVEAN

Benign

-0.75

N;N

REVEL

Benign

0.16

Sift

Uncertain

0.015

D;D

Sift4G

Benign

0.54

T;T

Polyphen

0.96

D;D

Vest4

0.12

MutPred

0.52

Loss of phosphorylation at Y212 (P = 0.0367);Loss of phosphorylation at Y212 (P = 0.0367);

MVP

0.072

MPC

0.025

ClinPred

0.097

GERP RS

0.86

Varity_R

0.15

gMVP

0.28

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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