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GeneBe

9-133670615-G-A

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

Scores

1
7
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.08
Variant links:
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]

Genome browser will be placed here

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
SARDHNM_001134707.2 linkuse as main transcriptc.2464C>T p.Arg822Cys missense_variant 19/21 ENST00000439388.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SARDHENST00000439388.6 linkuse as main transcriptc.2464C>T p.Arg822Cys missense_variant 19/212 NM_001134707.2 P1Q9UL12-1
SARDHENST00000371872.8 linkuse as main transcriptc.2464C>T p.Arg822Cys missense_variant 19/211 P1Q9UL12-1
SARDHENST00000371868.5 linkuse as main transcriptc.748C>T p.Arg250Cys missense_variant 7/92

Frequencies

GnomAD3 genomes
AF:
0.0000394
AC:
6
AN:
152212
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000965
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000533
AC:
10
AN:
187574
Hom.:
0
AF XY:
0.0000690
AC XY:
7
AN XY:
101518
show subpopulations
Gnomad AFR exome
AF:
0.000184
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000397
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000897
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000533
AC:
76
AN:
1426440
Hom.:
0
Cov.:
32
AF XY:
0.0000665
AC XY:
47
AN XY:
706362
show subpopulations
Gnomad4 AFR exome
AF:
0.000304
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000264
Gnomad4 SAS exome
AF:
0.000123
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000365
Gnomad4 OTH exome
AF:
0.000186
GnomAD4 genome
AF:
0.0000460
AC:
7
AN:
152330
Hom.:
0
Cov.:
33
AF XY:
0.0000671
AC XY:
5
AN XY:
74492
show subpopulations
Gnomad4 AFR
AF:
0.000120
Gnomad4 AMR
AF:
0.0000653
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000847
Hom.:
0
Bravo
AF:
0.0000227
ExAC
AF:
0.0000506
AC:
6
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

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 submitterclinical testingAmbry GeneticsJul 13, 2021The 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.073
BayesDel_addAF
Benign
-0.19
T
BayesDel_noAF
Benign
-0.23
CADD
Benign
22
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.74
D;D;.;D
Eigen
Benign
0.14
Eigen_PC
Benign
0.0018
FATHMM_MKL
Benign
0.073
N
M_CAP
Uncertain
0.28
D
MetaRNN
Benign
0.36
T;T;T;T
MetaSVM
Benign
-0.38
T
MutationAssessor
Pathogenic
3.1
M;.;.;M
MutationTaster
Benign
1.0
N;N;N;N
PrimateAI
Benign
0.39
T
PROVEAN
Uncertain
-4.0
D;D;.;D
REVEL
Uncertain
0.32
Sift
Uncertain
0.010
D;D;.;D
Sift4G
Uncertain
0.0070
D;D;D;D
Polyphen
0.98
D;D;.;D
Vest4
0.31
MutPred
0.53
Loss of MoRF binding (P = 0.0185);.;.;Loss of MoRF binding (P = 0.0185);
MVP
0.89
MPC
0.29
ClinPred
0.41
T
GERP RS
4.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.095
gMVP
0.75

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.

Other links and lift over

dbSNP: rs768116522; hg19: chr9-136535737; COSMIC: COSV100898354; COSMIC: COSV100898354; API