9-133663916-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001134707.2(SARDH):ā€‹c.2730C>Gā€‹(p.Asn910Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,614,068 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 33)
Exomes š‘“: 0.0000021 ( 0 hom. )

Consequence

SARDH
NM_001134707.2 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.802
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.118594676).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SARDHNM_001134707.2 linkc.2730C>G p.Asn910Lys missense_variant Exon 21 of 21 ENST00000439388.6 NP_001128179.1 Q9UL12-1A8K596

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SARDHENST00000439388.6 linkc.2730C>G p.Asn910Lys missense_variant Exon 21 of 21 2 NM_001134707.2 ENSP00000403084.1 Q9UL12-1
SARDHENST00000371872.8 linkc.2730C>G p.Asn910Lys missense_variant Exon 21 of 21 1 ENSP00000360938.4 Q9UL12-1
SARDHENST00000371868.5 linkc.1080C>G p.Asn360Lys missense_variant Exon 9 of 9 2 ENSP00000360934.1 Q5SYV2

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152204
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1461864
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
727228
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
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:
0.00000270
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152204
Hom.:
0
Cov.:
33
AF XY:
0.0000134
AC XY:
1
AN XY:
74366
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
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
Bravo
AF:
0.00000378

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Sep 02, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.2730C>G (p.N910K) alteration is located in exon 21 (coding exon 20) of the SARDH gene. This alteration results from a C to G substitution at nucleotide position 2730, causing the asparagine (N) at amino acid position 910 to be replaced by a lysine (K). 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
0.097
BayesDel_addAF
Benign
-0.12
T
BayesDel_noAF
Benign
-0.41
CADD
Benign
16
DANN
Benign
0.52
DEOGEN2
Benign
0.19
T;T;T
Eigen
Benign
-0.72
Eigen_PC
Benign
-0.49
FATHMM_MKL
Uncertain
0.79
D
LIST_S2
Benign
0.83
.;T;D
M_CAP
Benign
0.031
D
MetaRNN
Benign
0.12
T;T;T
MetaSVM
Benign
-0.84
T
MutationAssessor
Benign
-0.41
N;.;N
PrimateAI
Benign
0.40
T
PROVEAN
Benign
0.24
N;N;N
REVEL
Benign
0.17
Sift
Benign
0.76
T;T;T
Sift4G
Benign
1.0
T;T;T
Polyphen
0.0
B;B;B
Vest4
0.17
MutPred
0.30
Gain of methylation at N910 (P = 0.0262);.;Gain of methylation at N910 (P = 0.0262);
MVP
0.53
MPC
0.24
ClinPred
0.21
T
GERP RS
3.7
Varity_R
0.16
gMVP
0.52

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: rs1829965903; hg19: chr9-136529038; API