rs129886

Variant names:

• chr9-133663599-C-T
• rs129886
• NM_001134707.2:c.*290G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 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: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001134707.2. 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.*290G>A		3_prime_UTR	Exon 21 of 21	NP_001128179.1	Q9UL12-1
	SARDH	NM_007101.4		c.*290G>A		3_prime_UTR	Exon 21 of 21	NP_009032.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SARDH	ENST00000439388.6	TSL:2 MANE Select	c.*290G>A		3_prime_UTR	Exon 21 of 21	ENSP00000403084.1	Q9UL12-1
	SARDH	ENST00000371872.8	TSL:1	c.*290G>A		3_prime_UTR	Exon 21 of 21	ENSP00000360938.4	Q9UL12-1
	SARDH	ENST00000859366.1		c.*290G>A		3_prime_UTR	Exon 22 of 22	ENSP00000529425.1

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

African (AFR) AF: 0.295 AC: 2614 AN: 8876

American (AMR) AF: 0.268 AC: 2558 AN: 9548

Ashkenazi Jewish (ASJ) AF: 0.187 AC: 1825 AN: 9768

East Asian (EAS) AF: 0.413 AC: 8507 AN: 20608

South Asian (SAS) AF: 0.279 AC: 5133 AN: 18422

European-Finnish (FIN) AF: 0.152 AC: 2502 AN: 16512

Middle Eastern (MID) AF: 0.233 AC: 309 AN: 1324

European-Non Finnish (NFE) AF: 0.189 AC: 31881 AN: 168792

Other (OTH) AF: 0.216 AC: 3758 AN: 17402

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

African (AFR) AF: 0.301 AC: 12490 AN: 41542

American (AMR) AF: 0.242 AC: 3710 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 646 AN: 3472

East Asian (EAS) AF: 0.396 AC: 2047 AN: 5172

South Asian (SAS) AF: 0.300 AC: 1448 AN: 4820

European-Finnish (FIN) AF: 0.150 AC: 1587 AN: 10602

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.193 AC: 13159 AN: 68006

Other (OTH) AF: 0.222 AC: 470 AN: 2114

Alfa AF: 0.212 Hom.: 13916

Bravo AF: 0.245

Asia WGS AF: 0.335 AC: 1165 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.8
DANN	Benign	0.50
PhyloP100		-0.23
Mutation Taster		=100/0	polymorphism (auto)

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: rs129886; hg19: chr9-136528721;