NM_001134707.2:c.2345C>T

Variant names:

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001134707.2(SARDH):c.2345C>T(p.Ala782Val) variant causes a missense change. The variant allele was found at a frequency of 0.00304 in 1,585,754 control chromosomes in the GnomAD database, including 13 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 Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. A782A) has been classified as Benign.

Frequency

Genomes: 𝑓 0.0026 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0031 ( 11 hom. )

Consequence

SARDH
NM_001134707.2 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 4.58

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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.017976671).

BP6

Variant 9-133670734-G-A is Benign according to our data. Variant chr9-133670734-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 718828.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SARDH	NM_001134707.2 link	c.2345C>T	p.Ala782Val	missense_variant	Exon 19 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.2345C>T	p.Ala782Val	missense_variant	Exon 19 of 21	2	NM_001134707.2	ENSP00000403084.1	Q9UL12-1
SARDH	ENST00000371872.8 link	c.2345C>T	p.Ala782Val	missense_variant	Exon 19 of 21	1		ENSP00000360938.4	Q9UL12-1
SARDH	ENST00000371868.5 link	c.629C>T	p.Ala210Val	missense_variant	Exon 7 of 9	2		ENSP00000360934.1	Q5SYV2

Frequencies

GnomAD3 genomes

AF:

0.00261

AC:

398

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000651

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00706

Gnomad ASJ

AF:

0.0109

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000827

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00313

Gnomad OTH

AF:

0.00334

GnomAD3 exomes

AF:

0.00285

AC:

610

AN:

213774

Hom.:

AF XY:

0.00272

AC XY:

319

AN XY:

117200

show subpopulations

Gnomad AFR exome

AF:

0.000495

Gnomad AMR exome

AF:

0.00508

Gnomad ASJ exome

AF:

0.0140

Gnomad EAS exome

AF:

0.000117

Gnomad SAS exome

AF:

0.000675

Gnomad FIN exome

AF:

0.0000535

Gnomad NFE exome

AF:

0.00319

Gnomad OTH exome

AF:

0.00392

GnomAD4 exome

AF:

0.00309

AC:

4429

AN:

1433418

Hom.:

Cov.:

AF XY:

0.00298

AC XY:

2121

AN XY:

710896

show subpopulations

Gnomad4 AFR exome

AF:

0.000462

Gnomad4 AMR exome

AF:

0.00537

Gnomad4 ASJ exome

AF:

0.0118

Gnomad4 EAS exome

AF:

0.0000763

Gnomad4 SAS exome

AF:

0.000611

Gnomad4 FIN exome

AF:

0.0000590

Gnomad4 NFE exome

AF:

0.00329

Gnomad4 OTH exome

AF:

0.00398

GnomAD4 genome

AF:

0.00261

AC:

397

AN:

152336

Hom.:

Cov.:

AF XY:

0.00209

AC XY:

156

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.000650

Gnomad4 AMR

AF:

0.00699

Gnomad4 ASJ

AF:

0.0109

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000827

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.00313

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00273

Hom.:

Bravo

AF:

0.00320

ESP6500AA

AF:

0.000695

AC:

ESP6500EA

AF:

0.00294

AC:

ExAC

AF:

0.00255

AC:

305

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Jul 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

SARDH: BP4, BS2 -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Benign

0.70

DEOGEN2

Uncertain

0.42

T;D;.;T

Eigen

Benign

-0.86

Eigen_PC

Benign

-0.84

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.78

.;T;T;T

MetaRNN

Benign

0.018

T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.8

L;.;.;L

PrimateAI

Benign

0.43

PROVEAN

Benign

-2.0

N;N;.;N

REVEL

Benign

0.22

Sift

Benign

0.50

T;T;.;T

Sift4G

Benign

0.50

T;T;T;T

Polyphen

0.34

B;B;.;B

Vest4

0.43

MVP

0.56

MPC

0.58

ClinPred

0.062

GERP RS

0.80

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.099

gMVP

0.84

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