Variant 9-133663914-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001134707.2(SARDH):c.2732A>G(p.Asn911Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,850 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SARDH
NM_001134707.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.24

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.30876622).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SARDH	NM_001134707.2 linkuse as main transcript	c.2732A>G	p.Asn911Ser	missense_variant	21/21	ENST00000439388.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SARDH	ENST00000439388.6 linkuse as main transcript	c.2732A>G	p.Asn911Ser	missense_variant	21/21	2	NM_001134707.2	P1	Q9UL12-1
SARDH	ENST00000371872.8 linkuse as main transcript	c.2732A>G	p.Asn911Ser	missense_variant	21/21	1		P1	Q9UL12-1
SARDH	ENST00000371868.5 linkuse as main transcript	c.1082A>G	p.Asn361Ser	missense_variant	9/9	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461850

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727222

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

Dec 20, 2021

The c.2732A>G (p.N911S) alteration is located in exon 21 (coding exon 20) of the SARDH gene. This alteration results from a A to G substitution at nucleotide position 2732, causing the asparagine (N) at amino acid position 911 to be replaced by a serine (S). 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

0.079

BayesDel_addAF

Benign

-0.039

BayesDel_noAF

Benign

-0.29

CADD

Benign

DANN

Benign

0.72

DEOGEN2

Benign

0.36

T;T;T

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.22

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.89

.;D;D

M_CAP

Benign

0.072

MetaRNN

Benign

0.31

T;T;T

MetaSVM

Benign

-0.56

MutationAssessor

Benign

1.9

L;.;L

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Benign

0.47

PROVEAN

Uncertain

-2.5

N;N;N

REVEL

Uncertain

0.32

Sift

Benign

0.15

T;T;T

Sift4G

Benign

0.31

T;T;T

Polyphen

0.74

P;P;P

Vest4

0.33

MutPred

0.33

Gain of phosphorylation at N911 (P = 0.0576);.;Gain of phosphorylation at N911 (P = 0.0576);

MVP

0.73

MPC

0.32

ClinPred

0.82

GERP RS

3.5

Varity_R

0.092

gMVP

0.66

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