rs129886

Positions:

• chr9-133663599-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001134707.2(SARDH):​c.*290G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 423,486 control chromosomes in the GnomAD database, including 11,791 homozygotes. 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: 𝑓 0.23 (4487 hom., cov: 33)
  • Exomes 𝑓: 0.22 (7304 hom.)
• Consequence: SARDH NM_001134707.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.231

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.382 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SARDH	NM_001134707.2	c.*290G>A		3_prime_UTR_variant	21/21	ENST00000439388.6	NP_001128179.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SARDH	ENST00000439388.6	c.*290G>A		3_prime_UTR_variant	21/21	2	NM_001134707.2	ENSP00000403084	P1
SARDH	ENST00000371872.8	c.*290G>A		3_prime_UTR_variant	21/21	1		ENSP00000360938	P1
SARDH	ENST00000371868.5	c.*290G>A		3_prime_UTR_variant	9/9	2		ENSP00000360934

Frequencies

GnomAD3 genomes AF: 0.234 AC: 35667 AN: 152116 Hom.: 4486 Cov.: 33

Gnomad AFR AF: 0.301

Gnomad AMI AF: 0.0866

Gnomad AMR AF: 0.242

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.396

Gnomad SAS AF: 0.301

Gnomad FIN AF: 0.150

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.193

Gnomad OTH AF: 0.224

GnomAD4 exome AF: 0.218 AC: 59087 AN: 271252 Hom.: 7304 Cov.: 3 AF XY: 0.220 AC XY: 30290 AN XY: 137732

Gnomad4 AFR exome AF: 0.295

Gnomad4 AMR exome AF: 0.268

Gnomad4 ASJ exome AF: 0.187

Gnomad4 EAS exome AF: 0.413

Gnomad4 SAS exome AF: 0.279

Gnomad4 FIN exome AF: 0.152

Gnomad4 NFE exome AF: 0.189

Gnomad4 OTH exome AF: 0.216

GnomAD4 genome AF: 0.234 AC: 35694 AN: 152234 Hom.: 4487 Cov.: 33 AF XY: 0.237 AC XY: 17644 AN XY: 74422

Gnomad4 AFR AF: 0.301

Gnomad4 AMR AF: 0.242

Gnomad4 ASJ AF: 0.186

Gnomad4 EAS AF: 0.396

Gnomad4 SAS AF: 0.300

Gnomad4 FIN AF: 0.150

Gnomad4 NFE AF: 0.193

Gnomad4 OTH AF: 0.222

Alfa AF: 0.203 Hom.: 5106

Bravo AF: 0.245

Asia WGS AF: 0.335 AC: 1165 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.8
DANN	Benign	0.50

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: rs129886; hg19: chr9-136528721;