chr9-133663916-G-T

Variant summary

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

The NM_001134707.2(SARDH):​c.2730C>A​(p.Asn910Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

SARDH
NM_001134707.2 missense

Scores

1
18

Clinical Significance

Not reported in ClinVar

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]

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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=0.11908612).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SARDHNM_001134707.2 linkc.2730C>A 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>A p.Asn910Lys missense_variant Exon 21 of 21 2 NM_001134707.2 ENSP00000403084.1 Q9UL12-1
SARDHENST00000371872.8 linkc.2730C>A p.Asn910Lys missense_variant Exon 21 of 21 1 ENSP00000360938.4 Q9UL12-1
SARDHENST00000371868.5 linkc.1080C>A p.Asn360Lys missense_variant Exon 9 of 9 2 ENSP00000360934.1 Q5SYV2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
6.84e-7
AC:
1
AN:
1461864
Hom.:
0
Cov.:
30
AF XY:
0.00000138
AC XY:
1
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

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
0.58
DEOGEN2
Benign
0.19
T;T;T
Eigen
Benign
-0.72
Eigen_PC
Benign
-0.49
FATHMM_MKL
Uncertain
0.81
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