chr9-133696245-G-T

Variant names:

• chr9-133696245-G-T
• rs2502740
• NM_001134707.2:c.1785C>A

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001134707.2(SARDH):​c.1785C>A​(p.Ser595Ser) variant causes a synonymous 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. Synonymous variant affecting the same amino acid position (i.e. S595S) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SARDH NM_001134707.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.51

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 Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP7: Synonymous conserved (PhyloP=-4.51 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SARDH	NM_001134707.2	c.1785C>A	p.Ser595Ser	synonymous_variant	Exon 14 of 21	ENST00000439388.6	NP_001128179.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SARDH	ENST00000439388.6	c.1785C>A	p.Ser595Ser	synonymous_variant	Exon 14 of 21	2	NM_001134707.2	ENSP00000403084.1
SARDH	ENST00000371872.8	c.1785C>A	p.Ser595Ser	synonymous_variant	Exon 14 of 21	1		ENSP00000360938.4
SARDH	ENST00000427237.6	c.1785C>A	p.Ser595Ser	synonymous_variant	Exon 14 of 15	2		ENSP00000394210.2
SARDH	ENST00000371868.5	c.69C>A	p.Ser23Ser	synonymous_variant	Exon 2 of 9	2		ENSP00000360934.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 51

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.010
DANN	Benign	0.36
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs2502740; hg19: chr9-136561367;