Variant 12-57229736-G-A 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.-43G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0111 in 1,613,708 control chromosomes in the GnomAD database, including 276 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.017 ( 46 hom., cov: 33)

Exomes 𝑓: 0.011 ( 230 hom. )

Consequence

SHMT2
NM_005412.6 5_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.92

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 (BayesDel_noAF=-0.73).

BP6

Variant 12-57229736-G-A is Benign according to our data. Variant chr12-57229736-G-A is described in ClinVar as [Benign]. Clinvar id is 1271323.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0633 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein	UniProt
SHMT2	NM_005412.6 linkuse as main transcript	c.-43G>A	5_prime_UTR_variant	1/12	ENST00000328923.8	NP_005403.2	P34897-1V9HW06Q5BJF5
SHMT2	NM_001166356.2 linkuse as main transcript	c.-43G>A	5_prime_UTR_variant	1/12		NP_001159828.1	P34897-2Q5BJF5
SHMT2	NR_029417.2 linkuse as main transcript	n.26G>A	non_coding_transcript_exon_variant	1/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SHMT2	ENST00000328923 linkuse as main transcript	c.-43G>A		5_prime_UTR_variant	1/12	1	NM_005412.6	ENSP00000333667.3		P34897-1

Frequencies

GnomAD3 genomes

AF:

0.0169

AC:

2569

AN:

152246

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0359

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00537

Gnomad ASJ

AF:

0.00230

Gnomad EAS

AF:

0.0691

Gnomad SAS

AF:

0.0238

Gnomad FIN

AF:

0.00104

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00698

Gnomad OTH

AF:

0.0134

GnomAD3 exomes

AF:

0.0133

AC:

3350

AN:

251126

Hom.:

AF XY:

0.0133

AC XY:

1800

AN XY:

135768

show subpopulations

Gnomad AFR exome

AF:

0.0361

Gnomad AMR exome

AF:

0.00330

Gnomad ASJ exome

AF:

0.00457

Gnomad EAS exome

AF:

0.0651

Gnomad SAS exome

AF:

0.0212

Gnomad FIN exome

AF:

0.00189

Gnomad NFE exome

AF:

0.00584

Gnomad OTH exome

AF:

0.00865

GnomAD4 exome

AF:

0.0105

AC:

15392

AN:

1461342

Hom.:

230

Cov.:

AF XY:

0.0107

AC XY:

7776

AN XY:

727038

show subpopulations

Gnomad4 AFR exome

AF:

0.0408

Gnomad4 AMR exome

AF:

0.00374

Gnomad4 ASJ exome

AF:

0.00566

Gnomad4 EAS exome

AF:

0.0697

Gnomad4 SAS exome

AF:

0.0213

Gnomad4 FIN exome

AF:

0.00154

Gnomad4 NFE exome

AF:

0.00737

Gnomad4 OTH exome

AF:

0.0127

GnomAD4 genome

AF:

0.0170

AC:

2591

AN:

152366

Hom.:

Cov.:

AF XY:

0.0177

AC XY:

1319

AN XY:

74510

show subpopulations

Gnomad4 AFR

AF:

0.0363

Gnomad4 AMR

AF:

0.00536

Gnomad4 ASJ

AF:

0.00230

Gnomad4 EAS

AF:

0.0692

Gnomad4 SAS

AF:

0.0240

Gnomad4 FIN

AF:

0.00104

Gnomad4 NFE

AF:

0.00698

Gnomad4 OTH

AF:

0.0132

Alfa

AF:

0.0102

Hom.:

Bravo

AF:

0.0184

Asia WGS

AF:

0.0560

AC:

193

AN:

3478

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 16, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

0.089

DANN

Benign

0.88

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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