Variant 9-133666739-C-T 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.2627G>A(p.Gly876Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000629 in 1,590,154 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000056 ( 0 hom. )

Consequence

SARDH
NM_001134707.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.99

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.2627G>A	p.Gly876Glu	missense_variant	20/21	ENST00000439388.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SARDH	ENST00000439388.6 linkuse as main transcript	c.2627G>A	p.Gly876Glu	missense_variant	20/21	2	NM_001134707.2	P1	Q9UL12-1
SARDH	ENST00000371872.8 linkuse as main transcript	c.2627G>A	p.Gly876Glu	missense_variant	20/21	1		P1	Q9UL12-1
SARDH	ENST00000371868.5 linkuse as main transcript	c.977G>A	p.Gly326Glu	missense_variant	8/9	2
SARDH	ENST00000469828.1 linkuse as main transcript	n.385G>A		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000285

AC:

AN:

210848

Hom.:

AF XY:

0.00

AC XY:

AN XY:

113720

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000198

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000556

AC:

AN:

1437932

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

713082

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000171

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.08e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152222

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000227

ExAC

AF:

0.0000166

AC:

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

Aug 26, 2022

The c.2627G>A (p.G876E) alteration is located in exon 20 (coding exon 19) of the SARDH gene. This alteration results from a G to A substitution at nucleotide position 2627, causing the glycine (G) at amino acid position 876 to be replaced by a glutamic acid (E). 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

0.083

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.17

CADD

Benign

DANN

Benign

0.88

DEOGEN2

Benign

0.24

T;T;T

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.58

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.68

.;T;T

M_CAP

Benign

0.060

MetaRNN

Benign

0.13

T;T;T

MetaSVM

Benign

-0.80

MutationAssessor

Benign

1.7

L;.;L

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Benign

0.48

PROVEAN

Benign

-0.92

N;N;N

REVEL

Uncertain

0.35

Sift

Benign

0.63

T;T;T

Sift4G

Benign

0.28

T;T;T

Polyphen

0.031

B;B;B

Vest4

0.32

MutPred

0.53

Gain of solvent accessibility (P = 0.012);.;Gain of solvent accessibility (P = 0.012);

MVP

0.64

MPC

0.29

ClinPred

0.065

GERP RS

3.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.4

Varity_R

0.090

gMVP

0.87

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.43

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.43

Position offset: 4

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