rs2229716

chr12-57232799-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.98

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]

ACMG classification

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	UniProt
SHMT2	NM_005412.6	c.813G>A	p.Ala271=	synonymous_variant	7/12	ENST00000328923.8

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0287 AC: 4365 AN: 152234 Hom.: 83 Cov.: 33

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

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.: 33 AF XY: 0.0361 AC XY: 26232 AN XY: 726742

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.: 83 Cov.: 33 AF XY: 0.0284 AC XY: 2116 AN XY: 74494

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.: 68

Bravo AF: 0.0290

Asia WGS AF: 0.00866 AC: 30 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

Other links and lift over

dbSNP: rs2229716; hg19: chr12-57626582; COSMIC: COSV61074282; COSMIC: COSV61074282;