Variant 12-57232235-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_005412.6(SHMT2):c.537C>T(p.Asp179Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0115 in 1,614,094 control chromosomes in the GnomAD database, including 333 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.017 ( 45 hom., cov: 33)

Exomes 𝑓: 0.011 ( 288 hom. )

Consequence

SHMT2
NM_005412.6 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.199

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.32).

BP6

Variant 12-57232235-C-T is Benign according to our data. Variant chr12-57232235-C-T is described in ClinVar as [Benign]. Clinvar id is 1248932.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.199 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0806 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.537C>T	p.Asp179Asp	synonymous_variant	5/12	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.537C>T	p.Asp179Asp	synonymous_variant	5/12	1	NM_005412.6	ENSP00000333667.3		P34897-1

Frequencies

GnomAD3 genomes

AF:

0.0167

AC:

2541

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0328

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00569

Gnomad ASJ

AF:

0.00230

Gnomad EAS

AF:

0.0870

Gnomad SAS

AF:

0.0214

Gnomad FIN

AF:

0.00104

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00716

Gnomad OTH

AF:

0.0139

GnomAD3 exomes

AF:

0.0137

AC:

3452

AN:

251448

Hom.:

AF XY:

0.0133

AC XY:

1813

AN XY:

135904

show subpopulations

Gnomad AFR exome

AF:

0.0329

Gnomad AMR exome

AF:

0.00324

Gnomad ASJ exome

AF:

0.00456

Gnomad EAS exome

AF:

0.0783

Gnomad SAS exome

AF:

0.0172

Gnomad FIN exome

AF:

0.00189

Gnomad NFE exome

AF:

0.00606

Gnomad OTH exome

AF:

0.00977

GnomAD4 exome

AF:

0.0109

AC:

15986

AN:

1461788

Hom.:

288

Cov.:

AF XY:

0.0109

AC XY:

7952

AN XY:

727206

show subpopulations

Gnomad4 AFR exome

AF:

0.0366

Gnomad4 AMR exome

AF:

0.00371

Gnomad4 ASJ exome

AF:

0.00563

Gnomad4 EAS exome

AF:

0.0927

Gnomad4 SAS exome

AF:

0.0181

Gnomad4 FIN exome

AF:

0.00155

Gnomad4 NFE exome

AF:

0.00745

Gnomad4 OTH exome

AF:

0.0126

GnomAD4 genome

AF:

0.0167

AC:

2544

AN:

152306

Hom.:

Cov.:

AF XY:

0.0177

AC XY:

1315

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.0328

Gnomad4 AMR

AF:

0.00568

Gnomad4 ASJ

AF:

0.00230

Gnomad4 EAS

AF:

0.0872

Gnomad4 SAS

AF:

0.0214

Gnomad4 FIN

AF:

0.00104

Gnomad4 NFE

AF:

0.00716

Gnomad4 OTH

AF:

0.0137

Alfa

AF:

0.00767

Hom.:

Bravo

AF:

0.0181

Asia WGS

AF:

0.0540

AC:

188

AN:

3478

EpiCase

AF:

0.00731

EpiControl

AF:

0.00545

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 05, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Uncertain

0.99

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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