rs573904

chr9-133734024-C-Achr9-133734024-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001134707.2(SARDH):c.150G>T(p.Gln50His) 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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. Q50Q) has been classified as Benign.

• Frequency: Genomes: not found (cov: 35)
• Consequence: SARDH NM_001134707.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.284

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]

ACMG classification

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=0.088195115).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SARDH	NM_001134707.2	c.150G>T	p.Gln50His	missense_variant	2/21	ENST00000439388.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SARDH	ENST00000439388.6	c.150G>T	p.Gln50His	missense_variant	2/21	2	NM_001134707.2	P1

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome Cov.: 49

GnomAD4 genome Cov.: 35

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
Cadd	Benign	3.0
Dann	Benign	0.90
DEOGEN2	Benign	0.28	T;T;T;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.072	N
M_CAP	Benign	0.077	D
MetaRNN	Benign	0.088	T;T;T;T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	1.9	M;M;.;.
MutationTaster	Benign	1.0	P;P;P;P;P
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.99	N;N;N;N
REVEL	Benign	0.13
Sift	Benign	0.080	T;T;T;D
Sift4G	Benign	0.10	T;T;.;T
Polyphen		0.51	P;P;.;.
Vest4		0.14
MutPred		0.16		Loss of helix (P = 0.079);Loss of helix (P = 0.079);Loss of helix (P = 0.079);Loss of helix (P = 0.079);
MVP		0.28
MPC		0.26
ClinPred		0.15	T
GERP RS		1.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.059
gMVP		0.42

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

Other links and lift over

dbSNP: rs573904; hg19: chr9-136599146;