Variant chr9-133694338-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_001134707.2(SARDH):c.1841G>A(p.Arg614His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.368 in 1,549,820 control chromosomes in the GnomAD database, including 106,118 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.36 ( 9977 hom., cov: 32)

Exomes 𝑓: 0.37 ( 96141 hom. )

Consequence

SARDH
NM_001134707.2 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.537

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0059126914).

BP6

Variant 9-133694338-C-T is Benign according to our data. Variant chr9-133694338-C-T is described in ClinVar as [Benign]. Clinvar id is 3059588.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.387 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.1841G>A	p.Arg614His	missense_variant	15/21	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.1841G>A	p.Arg614His	missense_variant	15/21	2	NM_001134707.2	ENSP00000403084	P1	Q9UL12-1
SARDH	ENST00000371872.8 linkuse as main transcript	c.1841G>A	p.Arg614His	missense_variant	15/21	1		ENSP00000360938	P1	Q9UL12-1
SARDH	ENST00000371868.5 linkuse as main transcript	c.125G>A	p.Arg42His	missense_variant	3/9	2		ENSP00000360934
SARDH	ENST00000427237.6 linkuse as main transcript			downstream_gene_variant		2		ENSP00000394210

Frequencies

GnomAD3 genomes

AF:

0.358

AC:

54381

AN:

151820

Hom.:

9966

Cov.:

show subpopulations

Gnomad AFR

AF:

0.299

Gnomad AMI

AF:

0.616

Gnomad AMR

AF:

0.395

Gnomad ASJ

AF:

0.332

Gnomad EAS

AF:

0.395

Gnomad SAS

AF:

0.326

Gnomad FIN

AF:

0.369

Gnomad MID

AF:

0.399

Gnomad NFE

AF:

0.382

Gnomad OTH

AF:

0.361

GnomAD3 exomes

AF:

0.378

AC:

58852

AN:

155762

Hom.:

11432

AF XY:

0.371

AC XY:

30408

AN XY:

82034

show subpopulations

Gnomad AFR exome

AF:

0.301

Gnomad AMR exome

AF:

0.458

Gnomad ASJ exome

AF:

0.335

Gnomad EAS exome

AF:

0.416

Gnomad SAS exome

AF:

0.323

Gnomad FIN exome

AF:

0.368

Gnomad NFE exome

AF:

0.378

Gnomad OTH exome

AF:

0.384

GnomAD4 exome

AF:

0.369

AC:

516392

AN:

1397882

Hom.:

96141

Cov.:

AF XY:

0.368

AC XY:

254029

AN XY:

689462

show subpopulations

Gnomad4 AFR exome

AF:

0.297

Gnomad4 AMR exome

AF:

0.458

Gnomad4 ASJ exome

AF:

0.334

Gnomad4 EAS exome

AF:

0.393

Gnomad4 SAS exome

AF:

0.325

Gnomad4 FIN exome

AF:

0.359

Gnomad4 NFE exome

AF:

0.372

Gnomad4 OTH exome

AF:

0.367

GnomAD4 genome

AF:

0.358

AC:

54415

AN:

151938

Hom.:

9977

Cov.:

AF XY:

0.357

AC XY:

26480

AN XY:

74258

show subpopulations

Gnomad4 AFR

AF:

0.299

Gnomad4 AMR

AF:

0.395

Gnomad4 ASJ

AF:

0.332

Gnomad4 EAS

AF:

0.395

Gnomad4 SAS

AF:

0.325

Gnomad4 FIN

AF:

0.369

Gnomad4 NFE

AF:

0.382

Gnomad4 OTH

AF:

0.356

Alfa

AF:

0.377

Hom.:

21877

Bravo

AF:

0.361

TwinsUK

AF:

0.365

AC:

1352

ALSPAC

AF:

0.366

AC:

1412

ESP6500AA

AF:

0.274

AC:

1056

ESP6500EA

AF:

0.345

AC:

2560

ExAC

AF:

0.253

AC:

10441

Asia WGS

AF:

0.366

AC:

1272

AN:

3476

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 18, 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

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.20

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.39

T;D;.;T

Eigen

Benign

-0.65

Eigen_PC

Benign

-0.72

FATHMM_MKL

Benign

0.099

LIST_S2

Benign

0.73

.;T;T;T

MetaRNN

Benign

0.0059

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

L;.;.;L

MutationTaster

Benign

1.0

P;P;P;P

PrimateAI

Benign

0.45

PROVEAN

Benign

-1.9

N;N;D;N

REVEL

Benign

0.20

Sift

Benign

0.077

T;T;D;T

Sift4G

Benign

0.16

T;T;T;T

Polyphen

0.98

D;B;.;D

Vest4

0.039

MPC

0.26

ClinPred

0.0065

GERP RS

2.7

Varity_R

0.076

gMVP

0.57

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