9-133694338-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_001134707.2(SARDH):c.1841G>A(p.Arg614His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.368 in 1,549,820 control chromosomes in the GnomAD database, including 106,118 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 Benign (no stars).

Frequency

Genomes: 𝑓 0.36 ( 9977 hom., cov: 32)

Exomes 𝑓: 0.37 ( 96141 hom. )

Consequence

SARDH
NM_001134707.2 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.537

Publications

37 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: Unknown, AR Classification: SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, ClinGen

SARDH links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0059126914).

BP6

Variant 9-133694338-C-T is Benign according to our data. Variant chr9-133694338-C-T is described in ClinVar as Benign. ClinVar VariationId is 3059588.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.387 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SARDH	NM_001134707.2 link	c.1841G>A	p.Arg614His	missense_variant	Exon 15 of 21	ENST00000439388.6	NP_001128179.1	Q9UL12-1A8K596

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SARDH	ENST00000439388.6 link	c.1841G>A	p.Arg614His	missense_variant	Exon 15 of 21	2	NM_001134707.2	ENSP00000403084.1	Q9UL12-1
SARDH	ENST00000371872.8 link	c.1841G>A	p.Arg614His	missense_variant	Exon 15 of 21	1		ENSP00000360938.4	Q9UL12-1
SARDH	ENST00000371868.5 link	c.125G>A	p.Arg42His	missense_variant	Exon 3 of 9	2		ENSP00000360934.1	Q5SYV2
SARDH	ENST00000427237.6 link	c.*16G>A		downstream_gene_variant		2		ENSP00000394210.2	Q5SYV1

Frequencies

GnomAD3 genomes

AF:

0.358

AC:

54381

AN:

151820

Hom.:

9966

Cov.:

show subpopulations

Gnomad AFR

AF:

0.299

Gnomad AMI

AF:

0.616

Gnomad AMR

AF:

0.395

Gnomad ASJ

AF:

0.332

Gnomad EAS

AF:

0.395

Gnomad SAS

AF:

0.326

Gnomad FIN

AF:

0.369

Gnomad MID

AF:

0.399

Gnomad NFE

AF:

0.382

Gnomad OTH

AF:

0.361

GnomAD2 exomes

AF:

0.378

AC:

58852

AN:

155762

AF XY:

0.371

show subpopulations

Gnomad AFR exome

AF:

0.301

Gnomad AMR exome

AF:

0.458

Gnomad ASJ exome

AF:

0.335

Gnomad EAS exome

AF:

0.416

Gnomad FIN exome

AF:

0.368

Gnomad NFE exome

AF:

0.378

Gnomad OTH exome

AF:

0.384

GnomAD4 exome

AF:

0.369

AC:

516392

AN:

1397882

Hom.:

96141

Cov.:

AF XY:

0.368

AC XY:

254029

AN XY:

689462

show subpopulations

African (AFR)

AF:

0.297

AC:

9388

AN:

31582

American (AMR)

AF:

0.458

AC:

16334

AN:

35678

Ashkenazi Jewish (ASJ)

AF:

0.334

AC:

8418

AN:

25166

East Asian (EAS)

AF:

0.393

AC:

14046

AN:

35726

South Asian (SAS)

AF:

0.325

AC:

25723

AN:

79216

European-Finnish (FIN)

AF:

0.359

AC:

17350

AN:

48358

Middle Eastern (MID)

AF:

0.415

AC:

2357

AN:

5678

European-Non Finnish (NFE)

AF:

0.372

AC:

401490

AN:

1078514

Other (OTH)

AF:

0.367

AC:

21286

AN:

57964

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

17510

35021

52531

70042

87552

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12822

25644

38466

51288

64110

<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:

0.358

AC:

54415

AN:

151938

Hom.:

9977

Cov.:

AF XY:

0.357

AC XY:

26480

AN XY:

74258

show subpopulations

African (AFR)

AF:

0.299

AC:

12391

AN:

41454

American (AMR)

AF:

0.395

AC:

6041

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.332

AC:

1153

AN:

3468

East Asian (EAS)

AF:

0.395

AC:

2037

AN:

5152

South Asian (SAS)

AF:

0.325

AC:

1555

AN:

4788

European-Finnish (FIN)

AF:

0.369

AC:

3888

AN:

10550

Middle Eastern (MID)

AF:

0.408

AC:

120

AN:

294

European-Non Finnish (NFE)

AF:

0.382

AC:

25920

AN:

67938

Other (OTH)

AF:

0.356

AC:

749

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1778

3556

5335

7113

8891

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

524

1048

1572

2096

2620

<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:

0.373

Hom.:

42573

Bravo

AF:

0.361

TwinsUK

AF:

0.365

AC:

1352

ALSPAC

AF:

0.366

AC:

1412

ESP6500AA

AF:

0.274

AC:

1056

ESP6500EA

AF:

0.345

AC:

2560

ExAC

AF:

0.253

AC:

10441

Asia WGS

AF:

0.366

AC:

1272

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

SARDH-related disorder

Benign:1

Oct 18, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.20

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.39

T;D;.;T

Eigen

Benign

-0.65

Eigen_PC

Benign

-0.72

FATHMM_MKL

Benign

0.099

LIST_S2

Benign

0.73

.;T;T;T

MetaRNN

Benign

0.0059

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

L;.;.;L

PhyloP100

0.54

PrimateAI

Benign

0.45

PROVEAN

Benign

-1.9

N;N;D;N

REVEL

Benign

0.20

Sift

Benign

0.077

T;T;D;T

Sift4G

Benign

0.16

T;T;T;T

Polyphen

0.98

D;B;.;D

Vest4

0.039

MPC

0.26

ClinPred

0.0065

GERP RS

2.7

Varity_R

0.076

gMVP

0.57

Mutation Taster

=98/2

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over