Variant 9-133670733-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_001134707.2(SARDH):c.2346G>A(p.Ala782=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00733 in 1,588,182 control chromosomes in the GnomAD database, including 67 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0054 ( 5 hom., cov: 33)

Exomes 𝑓: 0.0075 ( 62 hom. )

Consequence

SARDH
NM_001134707.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -5.98

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 -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 9-133670733-C-T is Benign according to our data. Variant chr9-133670733-C-T is described in ClinVar as [Benign]. Clinvar id is 791575.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-5.98 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SARDH	NM_001134707.2 linkuse as main transcript	c.2346G>A	p.Ala782=	synonymous_variant	19/21	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.2346G>A	p.Ala782=	synonymous_variant	19/21	2	NM_001134707.2	ENSP00000403084	P1	Q9UL12-1
SARDH	ENST00000371872.8 linkuse as main transcript	c.2346G>A	p.Ala782=	synonymous_variant	19/21	1		ENSP00000360938	P1	Q9UL12-1
SARDH	ENST00000371868.5 linkuse as main transcript	c.630G>A	p.Ala210=	synonymous_variant	7/9	2		ENSP00000360934

Frequencies

GnomAD3 genomes

AF:

0.00541

AC:

824

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00157

Gnomad AMI

AF:

0.00768

Gnomad AMR

AF:

0.00137

Gnomad ASJ

AF:

0.00288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00216

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0101

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00584

AC:

1265

AN:

216476

Hom.:

AF XY:

0.00583

AC XY:

693

AN XY:

118842

show subpopulations

Gnomad AFR exome

AF:

0.00204

Gnomad AMR exome

AF:

0.00150

Gnomad ASJ exome

AF:

0.00395

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000697

Gnomad FIN exome

AF:

0.00249

Gnomad NFE exome

AF:

0.0111

Gnomad OTH exome

AF:

0.00446

GnomAD4 exome

AF:

0.00753

AC:

10815

AN:

1435874

Hom.:

Cov.:

AF XY:

0.00736

AC XY:

5244

AN XY:

712418

show subpopulations

Gnomad4 AFR exome

AF:

0.00129

Gnomad4 AMR exome

AF:

0.00174

Gnomad4 ASJ exome

AF:

0.00346

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000729

Gnomad4 FIN exome

AF:

0.00357

Gnomad4 NFE exome

AF:

0.00909

Gnomad4 OTH exome

AF:

0.00570

GnomAD4 genome

AF:

0.00541

AC:

824

AN:

152308

Hom.:

Cov.:

AF XY:

0.00486

AC XY:

362

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.00156

Gnomad4 AMR

AF:

0.00137

Gnomad4 ASJ

AF:

0.00288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00216

Gnomad4 NFE

AF:

0.0101

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00769

Hom.:

Bravo

AF:

0.00528

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Feb 01, 2024	SARDH: BP4, BP7, BS1, BS2 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.14

DANN

Benign

0.78

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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