chr10-95202016-G-C
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
NM_207321.3 missense
Scores
4
2
12
Clinical Significance
Conservation
PhyloP100: 4.50
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]
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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 | UniProt |
---|---|---|---|---|---|---|---|
ACSM6 | NM_207321.3 | c.224G>C | p.Trp75Ser | missense_variant | 3/11 | ENST00000394005.4 | |
LOC107984257 | XR_007062253.1 | n.347+23532C>G | intron_variant, non_coding_transcript_variant | ||||
ACSM6 | XM_047424638.1 | c.224G>C | p.Trp75Ser | missense_variant | 3/10 | ||
ACSM6 | XM_047424639.1 | c.224G>C | p.Trp75Ser | missense_variant | 2/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ACSM6 | ENST00000394005.4 | c.224G>C | p.Trp75Ser | missense_variant | 3/11 | 5 | NM_207321.3 | P1 | |
ACSM6 | ENST00000404473.6 | c.*47G>C | 3_prime_UTR_variant, NMD_transcript_variant | 3/10 | 1 | ||||
ACSM6 | ENST00000327739.7 | c.224G>C | p.Trp75Ser | missense_variant, NMD_transcript_variant | 3/9 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD3 exomes AF: 0.0000191 AC: 3AN: 156702Hom.: 0 AF XY: 0.0000241 AC XY: 2AN XY: 82968
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GnomAD4 exome AF: 0.00000214 AC: 3AN: 1399464Hom.: 0 Cov.: 32 AF XY: 0.00000290 AC XY: 2AN XY: 690238
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GnomAD4 genome ? Cov.: 32
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?
Cov.:
32
Bravo
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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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
DEOGEN2
Benign
T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;.
M_CAP
Benign
T
MetaRNN
Pathogenic
D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M
MutationTaster
Benign
D;N;N
PROVEAN
Pathogenic
D;D
REVEL
Benign
Sift
Pathogenic
D;D
Sift4G
Uncertain
D;D
Polyphen
D;D
Vest4
MutPred
Gain of disorder (P = 2e-04);Gain of disorder (P = 2e-04);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at