Variant rs2229716 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_005412.6(SHMT2):c.813G>A(p.Ala271=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0361 in 1,613,500 control chromosomes in the GnomAD database, including 1,210 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.029 ( 83 hom., cov: 33)

Exomes 𝑓: 0.037 ( 1127 hom. )

Consequence

SHMT2
NM_005412.6 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.98

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.64).

BP7

Synonymous conserved (PhyloP=-1.98 with no splicing effect.

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0704 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.813G>A	p.Ala271=	synonymous_variant	7/12	ENST00000328923.8	NP_005403.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SHMT2	ENST00000328923.8 linkuse as main transcript	c.813G>A	p.Ala271=	synonymous_variant	7/12	1	NM_005412.6	ENSP00000333667	P1	P34897-1

Frequencies

GnomAD3 genomes

AF:

0.0287

AC:

4365

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00685

Gnomad AMI

AF:

0.103

Gnomad AMR

AF:

0.0322

Gnomad ASJ

AF:

0.0308

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.0132

Gnomad FIN

AF:

0.0329

Gnomad MID

AF:

0.111

Gnomad NFE

AF:

0.0419

Gnomad OTH

AF:

0.0415

GnomAD3 exomes

AF:

0.0296

AC:

7447

AN:

251246

Hom.:

156

AF XY:

0.0296

AC XY:

4026

AN XY:

135820

show subpopulations

Gnomad AFR exome

AF:

0.00720

Gnomad AMR exome

AF:

0.0221

Gnomad ASJ exome

AF:

0.0314

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0140

Gnomad FIN exome

AF:

0.0330

Gnomad NFE exome

AF:

0.0427

Gnomad OTH exome

AF:

0.0414

GnomAD4 exome

AF:

0.0369

AC:

53852

AN:

1461148

Hom.:

1127

Cov.:

AF XY:

0.0361

AC XY:

26232

AN XY:

726742

show subpopulations

Gnomad4 AFR exome

AF:

0.00786

Gnomad4 AMR exome

AF:

0.0245

Gnomad4 ASJ exome

AF:

0.0318

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0157

Gnomad4 FIN exome

AF:

0.0331

Gnomad4 NFE exome

AF:

0.0413

Gnomad4 OTH exome

AF:

0.0360

GnomAD4 genome

AF:

0.0286

AC:

4364

AN:

152352

Hom.:

Cov.:

AF XY:

0.0284

AC XY:

2116

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.00683

Gnomad4 AMR

AF:

0.0322

Gnomad4 ASJ

AF:

0.0308

Gnomad4 EAS

AF:

0.000578

Gnomad4 SAS

AF:

0.0133

Gnomad4 FIN

AF:

0.0329

Gnomad4 NFE

AF:

0.0419

Gnomad4 OTH

AF:

0.0411

Alfa

AF:

0.0367

Hom.:

Bravo

AF:

0.0290

Asia WGS

AF:

0.00866

AC:

AN:

3478

EpiCase

AF:

0.0455

EpiControl

AF:

0.0449

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

5.8

DANN

Benign

0.80

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over