9-133666770-C-A

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_001134707.2(SARDH):​c.2596G>T​(p.Ala866Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000069 in 1,448,852 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

SARDH
NM_001134707.2 missense

Scores

5
9
5

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.49
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 Likely_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.967

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SARDHNM_001134707.2 linkc.2596G>T p.Ala866Ser missense_variant Exon 20 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.2596G>T p.Ala866Ser missense_variant Exon 20 of 21 2 NM_001134707.2 ENSP00000403084.1 Q9UL12-1
SARDHENST00000371872.8 linkc.2596G>T p.Ala866Ser missense_variant Exon 20 of 21 1 ENSP00000360938.4 Q9UL12-1
SARDHENST00000371868.5 linkc.946G>T p.Ala316Ser missense_variant Exon 8 of 9 2 ENSP00000360934.1 Q5SYV2
SARDHENST00000469828.1 linkn.354G>T non_coding_transcript_exon_variant Exon 1 of 2 2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.90e-7
AC:
1
AN:
1448852
Hom.:
0
Cov.:
32
AF XY:
0.00000139
AC XY:
1
AN XY:
719464
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:
0.0000119
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.18
BayesDel_addAF
Pathogenic
0.17
D
BayesDel_noAF
Uncertain
0.010
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.42
T;D;.;T
Eigen
Uncertain
0.57
Eigen_PC
Uncertain
0.50
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Benign
0.84
.;T;T;T
M_CAP
Pathogenic
0.37
D
MetaRNN
Pathogenic
0.96
D;D;D;D
MetaSVM
Uncertain
0.46
D
MutationAssessor
Pathogenic
3.4
M;.;.;M
PrimateAI
Benign
0.39
T
PROVEAN
Benign
-0.89
N;N;N;N
REVEL
Uncertain
0.62
Sift
Uncertain
0.017
D;D;T;D
Sift4G
Uncertain
0.014
D;D;D;D
Polyphen
0.95
P;P;.;P
Vest4
0.74
MutPred
0.82
Gain of disorder (P = 0.034);.;.;Gain of disorder (P = 0.034);
MVP
0.92
MPC
0.69
ClinPred
0.98
D
GERP RS
4.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.17
gMVP
0.87

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: rs778141547; hg19: chr9-136531892; API