chr10-95219892-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_207321.3(ACSM6):c.1121G>A(p.Gly374Asp) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000632 in 1,612,888 control chromosomes in the GnomAD database, with no homozygous occurrence. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000066 ( 0 hom. )
Consequence
ACSM6
NM_207321.3 missense, splice_region
NM_207321.3 missense, splice_region
Scores
4
14
Splicing: ADA: 0.00007715
2
Clinical Significance
Conservation
PhyloP100: 0.225
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 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ACSM6 | NM_207321.3 | c.1121G>A | p.Gly374Asp | missense_variant, splice_region_variant | 9/11 | ENST00000394005.4 | |
LOC107984257 | XR_007062253.1 | n.347+5656C>T | intron_variant, non_coding_transcript_variant | ||||
ACSM6 | XM_047424638.1 | c.1121G>A | p.Gly374Asp | missense_variant, splice_region_variant | 9/10 | ||
ACSM6 | XM_047424639.1 | c.1121G>A | p.Gly374Asp | missense_variant, splice_region_variant | 8/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ACSM6 | ENST00000394005.4 | c.1121G>A | p.Gly374Asp | missense_variant, splice_region_variant | 9/11 | 5 | NM_207321.3 | P1 | |
ACSM6 | ENST00000404473.6 | c.*944G>A | splice_region_variant, 3_prime_UTR_variant, NMD_transcript_variant | 9/10 | 1 | ||||
ACSM6 | ENST00000327739.7 | c.*561G>A | splice_region_variant, 3_prime_UTR_variant, NMD_transcript_variant | 8/9 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000395 AC: 6AN: 151990Hom.: 0 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000638 AC: 16AN: 250666Hom.: 0 AF XY: 0.0000591 AC XY: 8AN XY: 135458
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GnomAD4 exome AF: 0.0000657 AC: 96AN: 1460780Hom.: 0 Cov.: 30 AF XY: 0.0000743 AC XY: 54AN XY: 726730
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GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152108Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74386
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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 | Aug 13, 2021 | The c.1121G>A (p.G374D) alteration is located in exon 9 (coding exon 8) of the ACSM6 gene. This alteration results from a G to A substitution at nucleotide position 1121, causing the glycine (G) at amino acid position 374 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
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
Uncertain
D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M
MutationTaster
Benign
N;N;N
PROVEAN
Uncertain
D;D
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
D;D
Vest4
MutPred
Loss of sheet (P = 0.1907);Loss of sheet (P = 0.1907);
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at