Variant 12-57230918-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005412.6(SHMT2):c.149C>T(p.Ser50Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0118 in 1,613,948 control chromosomes in the GnomAD database, including 304 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.027 ( 131 hom., cov: 33)

Exomes 𝑓: 0.010 ( 173 hom. )

Consequence

SHMT2
NM_005412.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.38

Variant links:

Genes affected

SHMT2 (HGNC:10852): (serine hydroxymethyltransferase 2) This gene encodes the mitochondrial form of a pyridoxal phosphate-dependent enzyme that catalyzes the reversible reaction of serine and tetrahydrofolate to glycine and 5,10-methylene tetrahydrofolate. The encoded product is primarily responsible for glycine synthesis. The activity of the encoded protein has been suggested to be the primary source of intracellular glycine. The gene which encodes the cytosolic form of this enzyme is located on chromosome 17. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]

SHMT2 links:

SHMT2 (HGNC:):

SHMT2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0030794144).

BP6

Variant 12-57230918-C-T is Benign according to our data. Variant chr12-57230918-C-T is described in ClinVar as [Benign]. Clinvar id is 1272337.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0767 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SHMT2	NM_005412.6 linkuse as main transcript	c.149C>T	p.Ser50Leu	missense_variant	2/12	ENST00000328923.8	NP_005403.2	P34897-1V9HW06Q5BJF5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SHMT2	ENST00000328923.8 linkuse as main transcript	c.149C>T	p.Ser50Leu	missense_variant	2/12	1	NM_005412.6	ENSP00000333667.3		P34897-1

Frequencies

GnomAD3 genomes

AF:

0.0274

AC:

4161

AN:

152026

Hom.:

131

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0789

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0112

Gnomad ASJ

AF:

0.0156

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.00236

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00866

Gnomad OTH

AF:

0.0211

GnomAD3 exomes

AF:

0.0115

AC:

2886

AN:

251410

Hom.:

AF XY:

0.00999

AC XY:

1358

AN XY:

135900

show subpopulations

Gnomad AFR exome

AF:

0.0791

Gnomad AMR exome

AF:

0.00587

Gnomad ASJ exome

AF:

0.0115

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00183

Gnomad FIN exome

AF:

0.00342

Gnomad NFE exome

AF:

0.00962

Gnomad OTH exome

AF:

0.00929

GnomAD4 exome

AF:

0.0102

AC:

14902

AN:

1461804

Hom.:

173

Cov.:

AF XY:

0.00972

AC XY:

7069

AN XY:

727196

show subpopulations

Gnomad4 AFR exome

AF:

0.0844

Gnomad4 AMR exome

AF:

0.00651

Gnomad4 ASJ exome

AF:

0.0106

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00214

Gnomad4 FIN exome

AF:

0.00369

Gnomad4 NFE exome

AF:

0.00932

Gnomad4 OTH exome

AF:

0.0111

GnomAD4 genome

AF:

0.0274

AC:

4173

AN:

152144

Hom.:

131

Cov.:

AF XY:

0.0259

AC XY:

1926

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.0790

Gnomad4 AMR

AF:

0.0112

Gnomad4 ASJ

AF:

0.0156

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00187

Gnomad4 FIN

AF:

0.00236

Gnomad4 NFE

AF:

0.00865

Gnomad4 OTH

AF:

0.0209

Alfa

AF:

0.0127

Hom.:

Bravo

AF:

0.0308

TwinsUK

AF:

0.00944

AC:

ALSPAC

AF:

0.00727

AC:

ESP6500AA

AF:

0.0778

AC:

343

ESP6500EA

AF:

0.00837

AC:

ExAC

AF:

0.0129

AC:

1560

Asia WGS

AF:

0.00664

AC:

AN:

3478

EpiCase

AF:

0.00774

EpiControl

AF:

0.0103

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.16

T;.;.;.;.;T;.;.;.;.;T;.;T

Eigen

Benign

-0.39

Eigen_PC

Benign

-0.27

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.92

D;D;D;.;D;.;D;D;.;D;D;D;D

MetaRNN

Benign

0.0031

T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.53

N;N;.;.;.;.;.;.;.;.;.;.;.

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-2.0

N;N;N;N;N;N;N;N;N;N;N;N;N

REVEL

Benign

0.033

Sift

Benign

0.21

T;T;T;T;T;T;T;T;T;T;T;T;T

Sift4G

Benign

0.23

T;T;T;T;T;T;T;T;T;T;T;T;T

Polyphen

0.097

B;.;.;.;.;.;.;.;.;.;.;.;.

Vest4

0.054

MPC

0.44

ClinPred

0.017

GERP RS

3.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.18

gMVP

0.34

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