rs2502740

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr9-133696245-G-A
• chr9-133696245-G-C
• chr9-133696245-G-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001134707.2(SARDH):​c.1785C>T​(p.Ser595Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 1,613,708 control chromosomes in the GnomAD database, including 83,204 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. S595S) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.27 (6075 hom., cov: 32)
  • Exomes 𝑓: 0.32 (77129 hom.)
• Consequence: SARDH NM_001134707.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -4.51
• Publications: 15 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 9-133696245-G-A is Benign according to our data. Variant chr9-133696245-G-A is described in ClinVar as Benign. ClinVar VariationId is 1239038.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-4.51 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.334 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.1785C>T	p.Ser595Ser	synonymous	Exon 14 of 21	NP_001128179.1	Q9UL12-1
	SARDH	NM_007101.4		c.1785C>T	p.Ser595Ser	synonymous	Exon 14 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.1785C>T	p.Ser595Ser	synonymous	Exon 14 of 21	ENSP00000403084.1	Q9UL12-1
	SARDH	ENST00000371872.8	TSL:1	c.1785C>T	p.Ser595Ser	synonymous	Exon 14 of 21	ENSP00000360938.4	Q9UL12-1
	SARDH	ENST00000859366.1		c.1785C>T	p.Ser595Ser	synonymous	Exon 14 of 22	ENSP00000529425.1

Frequencies

GnomAD3 genomes AF: 0.270 AC: 40968 AN: 151930 Hom.: 6077 Cov.: 32

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.234

Gnomad AMR AF: 0.282

Gnomad ASJ AF: 0.368

Gnomad EAS AF: 0.114

Gnomad SAS AF: 0.214

Gnomad FIN AF: 0.334

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.337

Gnomad OTH AF: 0.305

GnomAD2 exomes AF: 0.278 AC: 69904 AN: 251106 AF XY: 0.283

Gnomad AFR exome AF: 0.138

Gnomad AMR exome AF: 0.197

Gnomad ASJ exome AF: 0.365

Gnomad EAS exome AF: 0.105

Gnomad FIN exome AF: 0.347

Gnomad NFE exome AF: 0.343

Gnomad OTH exome AF: 0.310

GnomAD4 exome AF: 0.319 AC: 466721 AN: 1461660 Hom.: 77129 Cov.: 51 AF XY: 0.318 AC XY: 230893 AN XY: 727144

African (AFR) AF: 0.141 AC: 4735 AN: 33480

American (AMR) AF: 0.201 AC: 8986 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.367 AC: 9590 AN: 26134

East Asian (EAS) AF: 0.123 AC: 4889 AN: 39700

South Asian (SAS) AF: 0.229 AC: 19736 AN: 86258

European-Finnish (FIN) AF: 0.352 AC: 18737 AN: 53296

Middle Eastern (MID) AF: 0.290 AC: 1673 AN: 5766

European-Non Finnish (NFE) AF: 0.341 AC: 379633 AN: 1111908

Other (OTH) AF: 0.310 AC: 18742 AN: 60394

GnomAD4 genome AF: 0.269 AC: 40973 AN: 152048 Hom.: 6075 Cov.: 32 AF XY: 0.271 AC XY: 20105 AN XY: 74322

African (AFR) AF: 0.153 AC: 6350 AN: 41466

American (AMR) AF: 0.282 AC: 4318 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.368 AC: 1278 AN: 3470

East Asian (EAS) AF: 0.114 AC: 587 AN: 5168

South Asian (SAS) AF: 0.214 AC: 1031 AN: 4812

European-Finnish (FIN) AF: 0.334 AC: 3535 AN: 10578

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.337 AC: 22930 AN: 67950

Other (OTH) AF: 0.308 AC: 649 AN: 2106

Alfa AF: 0.311 Hom.: 14750

Bravo AF: 0.260

EpiCase AF: 0.348

EpiControl AF: 0.349

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	SARDH-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.11
DANN	Benign	0.40
PhyloP100		-4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=98/2	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: rs2502740; hg19: chr9-136561367; COSMIC: COSV108211562;