Variant 9-133666831-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2

The NM_001134707.2(SARDH):c.2535C>T(p.Asn845=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000461 in 1,610,722 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00053 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00045 ( 2 hom. )

Consequence

SARDH
NM_001134707.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: -2.58

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 9-133666831-G-A is Benign according to our data. Variant chr9-133666831-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3043833.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-2.58 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SARDH	NM_001134707.2 linkuse as main transcript	c.2535C>T	p.Asn845=	synonymous_variant	20/21	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.2535C>T	p.Asn845=	synonymous_variant	20/21	2	NM_001134707.2	ENSP00000403084	P1	Q9UL12-1
SARDH	ENST00000371872.8 linkuse as main transcript	c.2535C>T	p.Asn845=	synonymous_variant	20/21	1		ENSP00000360938	P1	Q9UL12-1
SARDH	ENST00000371868.5 linkuse as main transcript	c.885C>T	p.Asn295=	synonymous_variant	8/9	2		ENSP00000360934
SARDH	ENST00000469828.1 linkuse as main transcript	n.293C>T		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes

AF:

0.000525

AC:

AN:

152254

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00443

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000529

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.000481

AC:

117

AN:

243054

Hom.:

AF XY:

0.000479

AC XY:

AN XY:

131632

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000913

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00189

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000236

Gnomad NFE exome

AF:

0.000430

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000454

AC:

662

AN:

1458350

Hom.:

Cov.:

AF XY:

0.000452

AC XY:

328

AN XY:

725096

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.000948

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00745

Gnomad4 SAS exome

AF:

0.0000117

Gnomad4 FIN exome

AF:

0.000247

Gnomad4 NFE exome

AF:

0.000256

Gnomad4 OTH exome

AF:

0.000348

GnomAD4 genome

AF:

0.000525

AC:

AN:

152372

Hom.:

Cov.:

AF XY:

0.000497

AC XY:

AN XY:

74516

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00444

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.000529

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.000371

Hom.:

Bravo

AF:

0.000695

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

SARDH-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 24, 2019

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

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Sep 01, 2024

SARDH: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

1.1

DANN

Benign

0.70

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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