ENST00000371867.5:c.-118G>T

Variant names:

• chr9-133734024-C-A
• rs573904
• ENST00000371867.5:c.-118G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000371867.5(SARDH):​c.-118G>T variant causes a 5 prime UTR premature start codon gain 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 35)
• Consequence: SARDH ENST00000371867.5 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.284
• Publications: 31 publications found

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]

SARDH Gene-Disease associations (from GenCC):

• sarcosinemia

  Inheritance: AR, Unknown Classification: MODERATE, SUPPORTIVE, LIMITED Submitted by: Orphanet, PanelApp Australia, ClinGen, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.088195115).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000371867.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SARDH	NM_001134707.2	MANE Select	c.150G>T	p.Gln50His	missense	Exon 2 of 21	NP_001128179.1	Q9UL12-1
	SARDH	NM_007101.4		c.150G>T	p.Gln50His	missense	Exon 2 of 21	NP_009032.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SARDH	ENST00000371867.5	TSL:1	c.-118G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 7	ENSP00000360933.1	Q5SYU9
	SARDH	ENST00000439388.6	TSL:2 MANE Select	c.150G>T	p.Gln50His	missense	Exon 2 of 21	ENSP00000403084.1	Q9UL12-1
	SARDH	ENST00000371872.8	TSL:1	c.150G>T	p.Gln50His	missense	Exon 2 of 21	ENSP00000360938.4	Q9UL12-1

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome Cov.: 49

GnomAD4 genome Cov.: 35

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.072	N
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.077	D
MetaRNN	Benign	0.088	T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	1.9	M
PhyloP100		-0.28
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.99	N
REVEL	Benign	0.13
Sift	Benign	0.080	T
Sift4G	Benign	0.10	T
Polyphen		0.51	P
Vest4		0.14
MutPred		0.16		Loss of helix (P = 0.079)
MVP		0.28
MPC		0.26
ClinPred		0.15	T
GERP RS		1.6
PromoterAI		0.012	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.059
gMVP		0.42
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs573904; hg19: chr9-136599146;