rs7301155

Variant names:

• chr12-57229038-G-A
• rs7301155
• ENST00000925589.1:c.-107-498G>A

Your query was ambiguous. Multiple possible variants found:

• chr12-57229038-G-A
• chr12-57229038-G-C
• chr12-57229038-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000925589.1(SHMT2):​c.-107-498G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.679 in 151,932 control chromosomes in the GnomAD database, including 35,216 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 0.68 (35216 hom., cov: 30)
• Consequence: SHMT2 ENST00000925589.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.205
• Publications: 13 publications found

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 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with cardiomyopathy, spasticity, and brain abnormalities

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: PanelApp Australia, ClinGen, G2P, Labcorp Genetics (formerly Invitae)
• complex neurodevelopmental disorder

  Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.742 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000925589.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHMT2	ENST00000925589.1		c.-107-498G>A		intron	N/A	ENSP00000595648.1
	SHMT2	ENST00000925590.1		c.-107-498G>A		intron	N/A	ENSP00000595649.1
	SHMT2	ENST00000925591.1		c.-107-498G>A		intron	N/A	ENSP00000595650.1

Frequencies

GnomAD3 genomes AF: 0.679 AC: 103051 AN: 151814 Hom.: 35184 Cov.: 30

Gnomad AFR AF: 0.723

Gnomad AMI AF: 0.608

Gnomad AMR AF: 0.619

Gnomad ASJ AF: 0.656

Gnomad EAS AF: 0.576

Gnomad SAS AF: 0.764

Gnomad FIN AF: 0.648

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.675

Gnomad OTH AF: 0.660

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.679 AC: 103129 AN: 151932 Hom.: 35216 Cov.: 30 AF XY: 0.678 AC XY: 50330 AN XY: 74226

African (AFR) AF: 0.723 AC: 29933 AN: 41424

American (AMR) AF: 0.619 AC: 9447 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.656 AC: 2277 AN: 3470

East Asian (EAS) AF: 0.577 AC: 2975 AN: 5156

South Asian (SAS) AF: 0.762 AC: 3660 AN: 4800

European-Finnish (FIN) AF: 0.648 AC: 6820 AN: 10530

Middle Eastern (MID) AF: 0.646 AC: 190 AN: 294

European-Non Finnish (NFE) AF: 0.675 AC: 45877 AN: 67972

Other (OTH) AF: 0.664 AC: 1400 AN: 2110

Alfa AF: 0.663 Hom.: 21870

Bravo AF: 0.667

Asia WGS AF: 0.643 AC: 2238 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.1
DANN	Benign	0.62
PhyloP100		-0.20

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7301155; hg19: chr12-57622821;