Genetic Variant NM_001134707.2:c.150G>A (chr9-133734024-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

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

The NM_001134707.2(SARDH):c.150G>A(p.Gln50Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 1,612,976 control chromosomes in the GnomAD database, including 67,396 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.24 ( 5000 hom., cov: 35)

Exomes 𝑓: 0.29 ( 62396 hom. )

Consequence

SARDH
NM_001134707.2 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.284

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=-0.83).

BP6

Variant 9-133734024-C-T is Benign according to our data. Variant chr9-133734024-C-T is described in ClinVar as [Benign]. Clinvar id is 3056141.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-0.284 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.296 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SARDH	NM_001134707.2 link	c.150G>A	p.Gln50Gln	synonymous_variant	Exon 2 of 21	ENST00000439388.6	NP_001128179.1	Q9UL12-1A8K596

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SARDH	ENST00000439388.6 link	c.150G>A	p.Gln50Gln	synonymous_variant	Exon 2 of 21	2	NM_001134707.2	ENSP00000403084.1		Q9UL12-1

Frequencies

GnomAD3 genomes

AF:

0.244

AC:

37170

AN:

152172

Hom.:

5002

Cov.:

show subpopulations

Gnomad AFR

AF:

0.127

Gnomad AMI

AF:

0.207

Gnomad AMR

AF:

0.242

Gnomad ASJ

AF:

0.264

Gnomad EAS

AF:

0.309

Gnomad SAS

AF:

0.232

Gnomad FIN

AF:

0.358

Gnomad MID

AF:

0.203

Gnomad NFE

AF:

0.295

Gnomad OTH

AF:

0.233

GnomAD3 exomes

AF:

0.268

AC:

66478

AN:

247690

Hom.:

9365

AF XY:

0.269

AC XY:

36273

AN XY:

134648

show subpopulations

Gnomad AFR exome

AF:

0.124

Gnomad AMR exome

AF:

0.224

Gnomad ASJ exome

AF:

0.266

Gnomad EAS exome

AF:

0.297

Gnomad SAS exome

AF:

0.217

Gnomad FIN exome

AF:

0.354

Gnomad NFE exome

AF:

0.296

Gnomad OTH exome

AF:

0.269

GnomAD4 exome

AF:

0.289

AC:

421980

AN:

1460686

Hom.:

62396

Cov.:

AF XY:

0.287

AC XY:

208748

AN XY:

726680

show subpopulations

Gnomad4 AFR exome

AF:

0.118

Gnomad4 AMR exome

AF:

0.224

Gnomad4 ASJ exome

AF:

0.266

Gnomad4 EAS exome

AF:

0.346

Gnomad4 SAS exome

AF:

0.227

Gnomad4 FIN exome

AF:

0.356

Gnomad4 NFE exome

AF:

0.298

Gnomad4 OTH exome

AF:

0.278

GnomAD4 genome

AF:

0.244

AC:

37169

AN:

152290

Hom.:

5000

Cov.:

AF XY:

0.247

AC XY:

18360

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.127

Gnomad4 AMR

AF:

0.242

Gnomad4 ASJ

AF:

0.264

Gnomad4 EAS

AF:

0.308

Gnomad4 SAS

AF:

0.231

Gnomad4 FIN

AF:

0.358

Gnomad4 NFE

AF:

0.295

Gnomad4 OTH

AF:

0.233

Alfa

AF:

0.282

Hom.:

11277

Bravo

AF:

0.232

Asia WGS

AF:

0.260

AC:

903

AN:

3478

EpiCase

AF:

0.290

EpiControl

AF:

0.292

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

SARDH-related disorder

Benign:1

Oct 22, 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

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.3

DANN

Benign

0.55

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