dbSNP rs2502740: SARDH:p.Ser595Ser (chr9-133696245-G-A) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001134707.2(SARDH):c.1785C>T(p.Ser595Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 1,613,708 control chromosomes in the GnomAD database, including 83,204 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.27 ( 6075 hom., cov: 32)

Exomes 𝑓: 0.32 ( 77129 hom. )

Consequence

SARDH
NM_001134707.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -4.51

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 9-133696245-G-A is Benign according to our data. Variant chr9-133696245-G-A is described in ClinVar as [Benign]. Clinvar id is 1239038.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-4.51 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.334 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SARDH	NM_001134707.2 link	c.1785C>T	p.Ser595Ser	synonymous_variant	Exon 14 of 21	ENST00000439388.6	NP_001128179.1	Q9UL12-1A8K596

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SARDH	ENST00000439388.6 link	c.1785C>T	p.Ser595Ser	synonymous_variant	Exon 14 of 21	2	NM_001134707.2	ENSP00000403084.1	Q9UL12-1
SARDH	ENST00000371872.8 link	c.1785C>T	p.Ser595Ser	synonymous_variant	Exon 14 of 21	1		ENSP00000360938.4	Q9UL12-1
SARDH	ENST00000427237.6 link	c.1785C>T	p.Ser595Ser	synonymous_variant	Exon 14 of 15	2		ENSP00000394210.2	Q5SYV1
SARDH	ENST00000371868.5 link	c.69C>T	p.Ser23Ser	synonymous_variant	Exon 2 of 9	2		ENSP00000360934.1	Q5SYV2

Frequencies

GnomAD3 genomes

AF:

0.270

AC:

40968

AN:

151930

Hom.:

6077

Cov.:

show subpopulations

Gnomad AFR

AF:

0.153

Gnomad AMI

AF:

0.234

Gnomad AMR

AF:

0.282

Gnomad ASJ

AF:

0.368

Gnomad EAS

AF:

0.114

Gnomad SAS

AF:

0.214

Gnomad FIN

AF:

0.334

Gnomad MID

AF:

0.291

Gnomad NFE

AF:

0.337

Gnomad OTH

AF:

0.305

GnomAD3 exomes

AF:

0.278

AC:

69904

AN:

251106

Hom.:

10774

AF XY:

0.283

AC XY:

38468

AN XY:

135756

show subpopulations

Gnomad AFR exome

AF:

0.138

Gnomad AMR exome

AF:

0.197

Gnomad ASJ exome

AF:

0.365

Gnomad EAS exome

AF:

0.105

Gnomad SAS exome

AF:

0.227

Gnomad FIN exome

AF:

0.347

Gnomad NFE exome

AF:

0.343

Gnomad OTH exome

AF:

0.310

GnomAD4 exome

AF:

0.319

AC:

466721

AN:

1461660

Hom.:

77129

Cov.:

AF XY:

0.318

AC XY:

230893

AN XY:

727144

show subpopulations

Gnomad4 AFR exome

AF:

0.141

Gnomad4 AMR exome

AF:

0.201

Gnomad4 ASJ exome

AF:

0.367

Gnomad4 EAS exome

AF:

0.123

Gnomad4 SAS exome

AF:

0.229

Gnomad4 FIN exome

AF:

0.352

Gnomad4 NFE exome

AF:

0.341

Gnomad4 OTH exome

AF:

0.310

GnomAD4 genome

AF:

0.269

AC:

40973

AN:

152048

Hom.:

6075

Cov.:

AF XY:

0.271

AC XY:

20105

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.153

Gnomad4 AMR

AF:

0.282

Gnomad4 ASJ

AF:

0.368

Gnomad4 EAS

AF:

0.114

Gnomad4 SAS

AF:

0.214

Gnomad4 FIN

AF:

0.334

Gnomad4 NFE

AF:

0.337

Gnomad4 OTH

AF:

0.308

Alfa

AF:

0.319

Hom.:

11631

Bravo

AF:

0.260

EpiCase

AF:

0.348

EpiControl

AF:

0.349

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Mar 11, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

SARDH-related disorder

Benign:1

Oct 28, 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

-0.93

CADD

Benign

0.11

DANN

Benign

0.40

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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