Variant 9-133671557-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_001134707.2(SARDH):c.2304C>T(p.Ile768=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.465 in 1,605,978 control chromosomes in the GnomAD database, including 178,125 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.51 ( 19917 hom., cov: 30)

Exomes 𝑓: 0.46 ( 158208 hom. )

Consequence

SARDH
NM_001134707.2 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.993

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BP6

Variant 9-133671557-G-A is Benign according to our data. Variant chr9-133671557-G-A is described in ClinVar as [Benign]. Clinvar id is 3059243.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=0.993 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.722 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SARDH	NM_001134707.2 linkuse as main transcript	c.2304C>T	p.Ile768=	synonymous_variant	18/21	ENST00000439388.6	NP_001128179.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SARDH	ENST00000439388.6 linkuse as main transcript	c.2304C>T	p.Ile768=	synonymous_variant	18/21	2	NM_001134707.2	ENSP00000403084	P1	Q9UL12-1
SARDH	ENST00000371872.8 linkuse as main transcript	c.2304C>T	p.Ile768=	synonymous_variant	18/21	1		ENSP00000360938	P1	Q9UL12-1
SARDH	ENST00000371868.5 linkuse as main transcript	c.588C>T	p.Ile196=	synonymous_variant	6/9	2		ENSP00000360934

Frequencies

GnomAD3 genomes

AF:

0.506

AC:

76688

AN:

151488

Hom.:

19909

Cov.:

show subpopulations

Gnomad AFR

AF:

0.588

Gnomad AMI

AF:

0.487

Gnomad AMR

AF:

0.566

Gnomad ASJ

AF:

0.424

Gnomad EAS

AF:

0.742

Gnomad SAS

AF:

0.471

Gnomad FIN

AF:

0.444

Gnomad MID

AF:

0.522

Gnomad NFE

AF:

0.443

Gnomad OTH

AF:

0.489

GnomAD3 exomes

AF:

0.504

AC:

119866

AN:

237862

Hom.:

31688

AF XY:

0.491

AC XY:

63407

AN XY:

129016

show subpopulations

Gnomad AFR exome

AF:

0.587

Gnomad AMR exome

AF:

0.668

Gnomad ASJ exome

AF:

0.411

Gnomad EAS exome

AF:

0.759

Gnomad SAS exome

AF:

0.457

Gnomad FIN exome

AF:

0.449

Gnomad NFE exome

AF:

0.431

Gnomad OTH exome

AF:

0.486

GnomAD4 exome

AF:

0.461

AC:

669871

AN:

1454372

Hom.:

158208

Cov.:

AF XY:

0.459

AC XY:

332096

AN XY:

722810

show subpopulations

Gnomad4 AFR exome

AF:

0.591

Gnomad4 AMR exome

AF:

0.658

Gnomad4 ASJ exome

AF:

0.415

Gnomad4 EAS exome

AF:

0.783

Gnomad4 SAS exome

AF:

0.456

Gnomad4 FIN exome

AF:

0.443

Gnomad4 NFE exome

AF:

0.439

Gnomad4 OTH exome

AF:

0.470

GnomAD4 genome

AF:

0.506

AC:

76741

AN:

151606

Hom.:

19917

Cov.:

AF XY:

0.508

AC XY:

37647

AN XY:

74070

show subpopulations

Gnomad4 AFR

AF:

0.588

Gnomad4 AMR

AF:

0.566

Gnomad4 ASJ

AF:

0.424

Gnomad4 EAS

AF:

0.742

Gnomad4 SAS

AF:

0.469

Gnomad4 FIN

AF:

0.444

Gnomad4 NFE

AF:

0.443

Gnomad4 OTH

AF:

0.486

Alfa

AF:

0.448

Hom.:

19038

Bravo

AF:

0.521

Asia WGS

AF:

0.584

AC:

2030

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

SARDH-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 2019

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

BayesDel_noAF

Benign

-0.49

CADD

Benign

6.0

DANN

Benign

0.63

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over