9-133670624-C-T

Position:

chr9-133670624-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001134707.2(SARDH):c.2455G>A(p.Ala819Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00281 in 1,579,404 control chromosomes in the GnomAD database, including 133 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.014 ( 70 hom., cov: 33)

Exomes 𝑓: 0.0016 ( 63 hom. )

Consequence

SARDH
NM_001134707.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.714

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00187096).

BP6

Variant 9-133670624-C-T is Benign according to our data. Variant chr9-133670624-C-T is described in ClinVar as [Benign]. Clinvar id is 776458.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0141 (2150/152314) while in subpopulation AFR AF= 0.0482 (2004/41562). AF 95% confidence interval is 0.0465. There are 70 homozygotes in gnomad4. There are 963 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 70 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SARDH	NM_001134707.2 linkuse as main transcript	c.2455G>A	p.Ala819Thr	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.2455G>A	p.Ala819Thr	missense_variant	19/21	2	NM_001134707.2	P1	Q9UL12-1
SARDH	ENST00000371872.8 linkuse as main transcript	c.2455G>A	p.Ala819Thr	missense_variant	19/21	1		P1	Q9UL12-1
SARDH	ENST00000371868.5 linkuse as main transcript	c.739G>A	p.Ala247Thr	missense_variant	7/9	2

Frequencies

GnomAD3 genomes

AF:

0.0141

AC:

2150

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0484

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00661

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000294

Gnomad OTH

AF:

0.0100

GnomAD3 exomes

AF:

0.00374

AC:

704

AN:

187998

Hom.:

AF XY:

0.00276

AC XY:

281

AN XY:

101844

show subpopulations

Gnomad AFR exome

AF:

0.0547

Gnomad AMR exome

AF:

0.00248

Gnomad ASJ exome

AF:

0.000114

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000793

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000395

Gnomad OTH exome

AF:

0.00142

GnomAD4 exome

AF:

0.00160

AC:

2287

AN:

1427090

Hom.:

Cov.:

AF XY:

0.00147

AC XY:

1041

AN XY:

706752

show subpopulations

Gnomad4 AFR exome

AF:

0.0512

Gnomad4 AMR exome

AF:

0.00279

Gnomad4 ASJ exome

AF:

0.0000786

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000110

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000252

Gnomad4 OTH exome

AF:

0.00325

GnomAD4 genome

AF:

0.0141

AC:

2150

AN:

152314

Hom.:

Cov.:

AF XY:

0.0129

AC XY:

963

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.0482

Gnomad4 AMR

AF:

0.00660

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000294

Gnomad4 OTH

AF:

0.00993

Alfa

AF:

0.00325

Hom.:

Bravo

AF:

0.0162

ESP6500AA

AF:

0.0457

AC:

197

ESP6500EA

AF:

0.000706

AC:

ExAC

AF:

0.00381

AC:

452

Asia WGS

AF:

0.00260

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.53

CADD

Benign

0.87

DANN

Benign

0.92

DEOGEN2

Benign

0.31

T;T;.;T

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.031

MetaRNN

Benign

0.0019

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

L;.;.;L

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.26

PROVEAN

Benign

0.080

N;N;.;N

REVEL

Benign

0.14

Sift

Benign

0.54

T;T;.;T

Sift4G

Benign

0.51

T;T;T;T

Polyphen

0.0010

B;B;.;B

Vest4

0.18

MVP

0.27

MPC

0.20

ClinPred

0.0050

GERP RS

-10

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.038

gMVP

0.52

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