Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001134707.2(SARDH):c.1540C>T(p.Arg514*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000968 in 1,579,968 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Affects (no stars). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00010 ( 0 hom. )

Consequence

SARDH
NM_001134707.2 stop_gained

Scores

Clinical Significance

Affects no assertion criteria provided O:1

Conservation

PhyloP100: 0.416

Publications

6 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: Uncertain_significance. The variant received 0 ACMG points.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SARDH	NM_001134707.2	MANE Select	c.1540C>T	p.Arg514*	stop_gained	Exon 12 of 21	NP_001128179.1
	SARDH	NM_007101.4		c.1540C>T	p.Arg514*	stop_gained	Exon 12 of 21	NP_009032.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SARDH	ENST00000439388.6	TSL:2 MANE Select	c.1540C>T	p.Arg514*	stop_gained	Exon 12 of 21	ENSP00000403084.1
SARDH	ENST00000371872.8	TSL:1	c.1540C>T	p.Arg514*	stop_gained	Exon 12 of 21	ENSP00000360938.4
SARDH	ENST00000427237.6	TSL:2	c.1540C>T	p.Arg514*	stop_gained	Exon 12 of 15	ENSP00000394210.2

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152078

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000725

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000112

AC:

AN:

196462

AF XY:

0.0000858

show subpopulations

Gnomad AFR exome

AF:

0.0000833

Gnomad AMR exome

AF:

0.000215

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000674

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000140

Gnomad OTH exome

AF:

0.000397

GnomAD4 exome

AF:

0.000102

AC:

146

AN:

1427772

Hom.:

Cov.:

AF XY:

0.000100

AC XY:

AN XY:

706650

show subpopulations

African (AFR)

AF:

0.0000302

AC:

AN:

33126

American (AMR)

AF:

0.000206

AC:

AN:

38790

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25398

East Asian (EAS)

AF:

0.00

AC:

AN:

38388

South Asian (SAS)

AF:

0.00

AC:

AN:

81210

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50386

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5510

European-Non Finnish (NFE)

AF:

0.000121

AC:

133

AN:

1095760

Other (OTH)

AF:

0.0000676

AC:

AN:

59204

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152196

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74416

show subpopulations

African (AFR)

AF:

0.0000723

AC:

AN:

41510

American (AMR)

AF:

0.000131

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

67976

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.000114

Hom.:

Bravo

AF:

0.0000831

ESP6500AA

AF:

0.000228

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000833

AC:

ClinVar

ClinVar submissions as Germline

Significance:Affects

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

Sarcosine dehydrogenase deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Pathogenic

0.26

CADD

Pathogenic

(source)

DANN

Uncertain

0.98

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.77

FATHMM_MKL

Benign

0.044

PhyloP100

0.42

Vest4

0.82

GERP RS

-3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=2/198

disease causing (fs/PTC)

(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.

chr9-133704962-G-A

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

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over