9-133670615-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_001134707.2(SARDH):c.2464C>T(p.Arg822Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000526 in 1,578,770 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000046 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000053 ( 0 hom. )
Consequence
SARDH
NM_001134707.2 missense
NM_001134707.2 missense
Scores
1
7
10
Clinical Significance
Conservation
PhyloP100: 1.08
Genes affected
SARDH (HGNC:10536): (sarcosine dehydrogenase) This gene encodes an enzyme localized to the mitochondrial matrix which catalyzes the oxidative demethylation of sarcosine. This enzyme is distinct from another mitochondrial matrix enzyme, dimethylglycine dehydrogenase, which catalyzes a reaction resulting in the formation of sarcosine. Mutations in this gene are associated with sarcosinemia. Alternatively spliced transcript variants have been described. [provided by RefSeq, Oct 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.36280406).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SARDH | NM_001134707.2 | c.2464C>T | p.Arg822Cys | missense_variant | 19/21 | ENST00000439388.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SARDH | ENST00000439388.6 | c.2464C>T | p.Arg822Cys | missense_variant | 19/21 | 2 | NM_001134707.2 | P1 | |
SARDH | ENST00000371872.8 | c.2464C>T | p.Arg822Cys | missense_variant | 19/21 | 1 | P1 | ||
SARDH | ENST00000371868.5 | c.748C>T | p.Arg250Cys | missense_variant | 7/9 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152212Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000533 AC: 10AN: 187574Hom.: 0 AF XY: 0.0000690 AC XY: 7AN XY: 101518
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GnomAD4 exome AF: 0.0000533 AC: 76AN: 1426440Hom.: 0 Cov.: 32 AF XY: 0.0000665 AC XY: 47AN XY: 706362
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GnomAD4 genome ? AF: 0.0000460 AC: 7AN: 152330Hom.: 0 Cov.: 33 AF XY: 0.0000671 AC XY: 5AN XY: 74492
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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 | Jul 13, 2021 | The c.2464C>T (p.R822C) alteration is located in exon 19 (coding exon 18) of the SARDH gene. This alteration results from a C to T substitution at nucleotide position 2464, causing the arginine (R) at amino acid position 822 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Uncertain
D;D;.;D
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
M_CAP
Uncertain
D
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Pathogenic
M;.;.;M
MutationTaster
Benign
N;N;N;N
PrimateAI
Benign
T
PROVEAN
Uncertain
D;D;.;D
REVEL
Uncertain
Sift
Uncertain
D;D;.;D
Sift4G
Uncertain
D;D;D;D
Polyphen
D;D;.;D
Vest4
MutPred
Loss of MoRF binding (P = 0.0185);.;.;Loss of MoRF binding (P = 0.0185);
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at