rs141409671

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001134707.2(SARDH):c.2345C>T(p.Ala782Val) variant causes a missense change. The variant allele was found at a frequency of 0.00304 in 1,585,754 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. A782A) has been classified as Benign.

Frequency

Genomes: 𝑓 0.0026 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0031 ( 11 hom. )

Consequence

SARDH
NM_001134707.2 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 4.58

Publications

3 publications found

Variant links:

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)

SARDH links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.017976671).

BP6

Variant 9-133670734-G-A is Benign according to our data. Variant chr9-133670734-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 718828.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 2 Unknown,AR gene

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.2345C>T	p.Ala782Val	missense	Exon 19 of 21	NP_001128179.1	Q9UL12-1
	SARDH	NM_007101.4		c.2345C>T	p.Ala782Val	missense	Exon 19 of 21	NP_009032.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SARDH	ENST00000439388.6	TSL:2 MANE Select	c.2345C>T	p.Ala782Val	missense	Exon 19 of 21	ENSP00000403084.1	Q9UL12-1
SARDH	ENST00000371872.8	TSL:1	c.2345C>T	p.Ala782Val	missense	Exon 19 of 21	ENSP00000360938.4	Q9UL12-1
SARDH	ENST00000859366.1		c.2525C>T	p.Ala842Val	missense	Exon 20 of 22	ENSP00000529425.1

Frequencies

GnomAD3 genomes

AF:

0.00261

AC:

398

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000651

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00706

Gnomad ASJ

AF:

0.0109

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000827

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00313

Gnomad OTH

AF:

0.00334

GnomAD2 exomes

AF:

0.00285

AC:

610

AN:

213774

AF XY:

0.00272

show subpopulations

Gnomad AFR exome

AF:

0.000495

Gnomad AMR exome

AF:

0.00508

Gnomad ASJ exome

AF:

0.0140

Gnomad EAS exome

AF:

0.000117

Gnomad FIN exome

AF:

0.0000535

Gnomad NFE exome

AF:

0.00319

Gnomad OTH exome

AF:

0.00392

GnomAD4 exome

AF:

0.00309

AC:

4429

AN:

1433418

Hom.:

Cov.:

AF XY:

0.00298

AC XY:

2121

AN XY:

710896

show subpopulations

African (AFR)

AF:

0.000462

AC:

AN:

32484

American (AMR)

AF:

0.00537

AC:

220

AN:

40988

Ashkenazi Jewish (ASJ)

AF:

0.0118

AC:

286

AN:

24168

East Asian (EAS)

AF:

0.0000763

AC:

AN:

39322

South Asian (SAS)

AF:

0.000611

AC:

AN:

81792

European-Finnish (FIN)

AF:

0.0000590

AC:

AN:

50872

Middle Eastern (MID)

AF:

0.000892

AC:

AN:

5604

European-Non Finnish (NFE)

AF:

0.00329

AC:

3612

AN:

1099186

Other (OTH)

AF:

0.00398

AC:

235

AN:

59002

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

276

553

829

1106

1382

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

142

284

426

568

710

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00261

AC:

397

AN:

152336

Hom.:

Cov.:

AF XY:

0.00209

AC XY:

156

AN XY:

74496

show subpopulations

African (AFR)

AF:

0.000650

AC:

AN:

41568

American (AMR)

AF:

0.00699

AC:

107

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.0109

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.000827

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.0000941

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00313

AC:

213

AN:

68022

Other (OTH)

AF:

0.00331

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00273

Hom.:

Bravo

AF:

0.00320

ESP6500AA

AF:

0.000695

AC:

ESP6500EA

AF:

0.00294

AC:

ExAC

AF:

0.00255

AC:

305

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.36

CADD

Benign

(source)

DANN

Benign

0.70

DEOGEN2

Uncertain

0.42

Eigen

Benign

-0.86

Eigen_PC

Benign

-0.84

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.78

MetaRNN

Benign

0.018

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.8

PhyloP100

4.6

PrimateAI

Benign

0.43

PROVEAN

Benign

-2.0

REVEL

Benign

0.22

Sift

Benign

0.50

Sift4G

Benign

0.50

Polyphen

0.34

Vest4

0.43

MVP

0.56

MPC

0.58

ClinPred

0.062

GERP RS

0.80

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.099

gMVP

0.84

Mutation Taster

=93/7

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over