NM_001134707.2:c.2455G>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001134707.2(SARDH):​c.2455G>T​(p.Ala819Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000701 in 1,427,100 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

SARDH
NM_001134707.2 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.714
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 Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.031157315).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SARDHNM_001134707.2 linkc.2455G>T p.Ala819Ser missense_variant Exon 19 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.2455G>T p.Ala819Ser missense_variant Exon 19 of 21 2 NM_001134707.2 ENSP00000403084.1 Q9UL12-1
SARDHENST00000371872.8 linkc.2455G>T p.Ala819Ser missense_variant Exon 19 of 21 1 ENSP00000360938.4 Q9UL12-1
SARDHENST00000371868.5 linkc.739G>T p.Ala247Ser missense_variant Exon 7 of 9 2 ENSP00000360934.1 Q5SYV2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
7.01e-7
AC:
1
AN:
1427100
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
706754
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:
9.13e-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
0.079
BayesDel_addAF
Benign
-0.20
T
BayesDel_noAF
Benign
-0.52
CADD
Benign
0.12
DANN
Benign
0.87
DEOGEN2
Benign
0.31
T;T;.;T
Eigen
Benign
-1.7
Eigen_PC
Benign
-1.7
FATHMM_MKL
Benign
0.040
N
LIST_S2
Benign
0.36
.;T;T;T
M_CAP
Benign
0.015
T
MetaRNN
Benign
0.031
T;T;T;T
MetaSVM
Benign
-0.95
T
MutationAssessor
Benign
0.89
L;.;.;L
PrimateAI
Benign
0.25
T
PROVEAN
Benign
0.52
N;N;.;N
REVEL
Benign
0.097
Sift
Benign
0.69
T;T;.;T
Sift4G
Benign
0.66
T;T;T;T
Polyphen
0.0020
B;B;.;B
Vest4
0.16
MutPred
0.37
Gain of disorder (P = 0.0455);.;.;Gain of disorder (P = 0.0455);
MVP
0.26
MPC
0.19
ClinPred
0.043
T
GERP RS
-10
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.044
gMVP
0.49

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-136535746; API