Variant 9-133670630-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001134707.2(SARDH):c.2449C>T(p.Arg817Trp) variant causes a missense change. The variant allele was found at a frequency of 0.000074 in 1,582,082 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 1 hom., cov: 33)

Exomes 𝑓: 0.000073 ( 0 hom. )

Consequence

SARDH
NM_001134707.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.38

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SARDH	NM_001134707.2 linkuse as main transcript	c.2449C>T	p.Arg817Trp	missense_variant	19/21	ENST00000439388.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SARDH	ENST00000439388.6 linkuse as main transcript	c.2449C>T	p.Arg817Trp	missense_variant	19/21	2	NM_001134707.2	P1	Q9UL12-1
SARDH	ENST00000371872.8 linkuse as main transcript	c.2449C>T	p.Arg817Trp	missense_variant	19/21	1		P1	Q9UL12-1
SARDH	ENST00000371868.5 linkuse as main transcript	c.733C>T	p.Arg245Trp	missense_variant	7/9	2

Frequencies

GnomAD3 genomes

AF:

0.0000788

AC:

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000141

AC:

AN:

191964

Hom.:

AF XY:

0.000154

AC XY:

AN XY:

104174

show subpopulations

Gnomad AFR exome

AF:

0.0000903

Gnomad AMR exome

AF:

0.0000345

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000824

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000494

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000734

AC:

105

AN:

1429888

Hom.:

Cov.:

AF XY:

0.0000918

AC XY:

AN XY:

708424

show subpopulations

Gnomad4 AFR exome

AF:

0.0000607

Gnomad4 AMR exome

AF:

0.0000249

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000757

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000328

Gnomad4 OTH exome

AF:

0.0000676

GnomAD4 genome

AF:

0.0000788

AC:

AN:

152194

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.000169

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00103

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000101

Hom.:

Bravo

AF:

0.0000907

ExAC

AF:

0.000126

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 20, 2021

The c.2449C>T (p.R817W) alteration is located in exon 19 (coding exon 18) of the SARDH gene. This alteration results from a C to T substitution at nucleotide position 2449, causing the arginine (R) at amino acid position 817 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.090

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.76

D;D;.;D

Eigen

Uncertain

0.65

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.96

.;D;D;D

M_CAP

Pathogenic

0.54

MetaRNN

Uncertain

0.50

D;D;D;D

MetaSVM

Uncertain

0.30

MutationAssessor

Pathogenic

3.2

M;.;.;M

MutationTaster

Benign

0.97

D;D;D;D

PrimateAI

Benign

0.41

PROVEAN

Pathogenic

-5.6

D;D;.;D

REVEL

Pathogenic

0.70

Sift

Uncertain

0.0010

D;D;.;D

Sift4G

Uncertain

0.0020

D;D;D;D

Polyphen

1.0

D;D;.;D

Vest4

0.39

MVP

0.92

MPC

0.73

ClinPred

0.93

GERP RS

4.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.53

gMVP

0.80

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