chr9-133734024-C-T

Variant names:

• chr9-133734024-C-T
• rs573904
• NM_001134707.2:c.150G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_001134707.2(SARDH):​c.150G>A​(p.Gln50Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 1,612,976 control chromosomes in the GnomAD database, including 67,396 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.24 (5000 hom., cov: 35)
  • Exomes 𝑓: 0.29 (62396 hom.)
• Consequence: SARDH NM_001134707.2 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• 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: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 9-133734024-C-T is Benign according to our data. Variant chr9-133734024-C-T is described in ClinVar as Benign. ClinVar VariationId is 3056141.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-0.284 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.296 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.150G>A	p.Gln50Gln	synonymous	Exon 2 of 21	NP_001128179.1	Q9UL12-1
	SARDH	NM_007101.4		c.150G>A	p.Gln50Gln	synonymous	Exon 2 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.150G>A	p.Gln50Gln	synonymous	Exon 2 of 21	ENSP00000403084.1	Q9UL12-1
	SARDH	ENST00000371872.8	TSL:1	c.150G>A	p.Gln50Gln	synonymous	Exon 2 of 21	ENSP00000360938.4	Q9UL12-1
	SARDH	ENST00000298628.6	TSL:1	c.150G>A	p.Gln50Gln	synonymous	Exon 2 of 7	ENSP00000298628.5	Q9UL10

Frequencies

GnomAD3 genomes AF: 0.244 AC: 37170 AN: 152172 Hom.: 5002 Cov.: 35

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.207

Gnomad AMR AF: 0.242

Gnomad ASJ AF: 0.264

Gnomad EAS AF: 0.309

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.358

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.295

Gnomad OTH AF: 0.233

GnomAD2 exomes AF: 0.268 AC: 66478 AN: 247690 AF XY: 0.269

Gnomad AFR exome AF: 0.124

Gnomad AMR exome AF: 0.224

Gnomad ASJ exome AF: 0.266

Gnomad EAS exome AF: 0.297

Gnomad FIN exome AF: 0.354

Gnomad NFE exome AF: 0.296

Gnomad OTH exome AF: 0.269

GnomAD4 exome AF: 0.289 AC: 421980 AN: 1460686 Hom.: 62396 Cov.: 49 AF XY: 0.287 AC XY: 208748 AN XY: 726680

African (AFR) AF: 0.118 AC: 3934 AN: 33474

American (AMR) AF: 0.224 AC: 10017 AN: 44688

Ashkenazi Jewish (ASJ) AF: 0.266 AC: 6959 AN: 26116

East Asian (EAS) AF: 0.346 AC: 13723 AN: 39682

South Asian (SAS) AF: 0.227 AC: 19552 AN: 86240

European-Finnish (FIN) AF: 0.356 AC: 18717 AN: 52538

Middle Eastern (MID) AF: 0.201 AC: 1153 AN: 5746

European-Non Finnish (NFE) AF: 0.298 AC: 331169 AN: 1111832

Other (OTH) AF: 0.278 AC: 16756 AN: 60370

GnomAD4 genome AF: 0.244 AC: 37169 AN: 152290 Hom.: 5000 Cov.: 35 AF XY: 0.247 AC XY: 18360 AN XY: 74460

African (AFR) AF: 0.127 AC: 5275 AN: 41586

American (AMR) AF: 0.242 AC: 3702 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.264 AC: 915 AN: 3472

East Asian (EAS) AF: 0.308 AC: 1596 AN: 5174

South Asian (SAS) AF: 0.231 AC: 1113 AN: 4822

European-Finnish (FIN) AF: 0.358 AC: 3800 AN: 10614

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.295 AC: 20028 AN: 67992

Other (OTH) AF: 0.233 AC: 492 AN: 2112

Alfa AF: 0.270 Hom.: 15945

Bravo AF: 0.232

Asia WGS AF: 0.260 AC: 903 AN: 3478

EpiCase AF: 0.290

EpiControl AF: 0.292

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	SARDH-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.3
DANN	Benign	0.55
PhyloP100		-0.28
PromoterAI		0.014	Neutral
Mutation Taster		=300/0	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: rs573904; hg19: chr9-136599146; COSMIC: COSV53833716; COSMIC: COSV53833716;