rs867823463

Variant names:

• chr9-133690384-C-G
• NM_001134707.2:c.2065G>C

Your query was ambiguous. Multiple possible variants found:

• chr9-133690384-C-G
• chr9-133690384-C-T

Variant summary

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

The NM_001134707.2(SARDH):​c.2065G>C​(p.Ala689Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,457,548 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SARDH NM_001134707.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.63

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SARDH	NM_001134707.2	c.2065G>C	p.Ala689Pro	missense_variant	Exon 16 of 21	ENST00000439388.6	NP_001128179.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SARDH	ENST00000439388.6	c.2065G>C	p.Ala689Pro	missense_variant	Exon 16 of 21	2	NM_001134707.2	ENSP00000403084.1
SARDH	ENST00000371872.8	c.2065G>C	p.Ala689Pro	missense_variant	Exon 16 of 21	1		ENSP00000360938.4
SARDH	ENST00000371868.5	c.349G>C	p.Ala117Pro	missense_variant	Exon 4 of 9	2		ENSP00000360934.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1457548 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 724492

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: 0.00000180

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	Uncertain	0.38
BayesDel_addAF	Uncertain	0.020	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.50	T;D;.;T
Eigen	Uncertain	0.23
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Benign	0.62	D
LIST_S2	Uncertain	0.93	.;D;D;D
M_CAP	Uncertain	0.18	D
MetaRNN	Uncertain	0.67	D;D;D;D
MetaSVM	Benign	-0.33	T
MutationAssessor	Benign	2.0	M;.;.;M
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.90	N;N;.;N
REVEL	Uncertain	0.40
Sift	Benign	0.11	T;T;.;T
Sift4G	Uncertain	0.055	T;T;T;T
Polyphen		0.49	P;P;.;P
Vest4		0.52
MutPred		0.56		Gain of glycosylation at A689 (P = 0.0144);.;.;Gain of glycosylation at A689 (P = 0.0144);
MVP		0.82
MPC		0.76
ClinPred		0.79	D
GERP RS		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.89
gMVP		0.86

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: chr9-136555506;