rs12937300

Positions:

• chr17-18330496-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004169.5(SHMT1):​c.1171+59A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 1,211,940 control chromosomes in the GnomAD database, including 52,107 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 0.26 (5606 hom., cov: 33)
  • Exomes 𝑓: 0.29 (46501 hom.)
• Consequence: SHMT1 NM_004169.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.76

Genes affected

SHMT1 (HGNC:10850): (serine hydroxymethyltransferase 1) This gene encodes the cytosolic form of serine hydroxymethyltransferase, a pyridoxal phosphate-containing enzyme that catalyzes the reversible conversion of serine and tetrahydrofolate to glycine and 5,10-methylene tetrahydrofolate. This reaction provides one-carbon units for synthesis of methionine, thymidylate, and purines in the cytoplasm. This gene is located within the Smith-Magenis syndrome region on chromosome 17. A pseudogene of this gene is located on the short arm of chromosome 1. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.309 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SHMT1	NM_004169.5	c.1171+59A>G		intron_variant		ENST00000316694.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SHMT1	ENST00000316694.8	c.1171+59A>G		intron_variant		1	NM_004169.5	P1

Frequencies

GnomAD3 genomes AF: 0.262 AC: 39879 AN: 151962 Hom.: 5607 Cov.: 33

Gnomad AFR AF: 0.206

Gnomad AMI AF: 0.319

Gnomad AMR AF: 0.228

Gnomad ASJ AF: 0.312

Gnomad EAS AF: 0.0726

Gnomad SAS AF: 0.182

Gnomad FIN AF: 0.323

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.312

Gnomad OTH AF: 0.257

GnomAD4 exome AF: 0.288 AC: 304985 AN: 1059860 Hom.: 46501 AF XY: 0.283 AC XY: 154487 AN XY: 545076

Gnomad4 AFR exome AF: 0.201

Gnomad4 AMR exome AF: 0.222

Gnomad4 ASJ exome AF: 0.314

Gnomad4 EAS exome AF: 0.0803

Gnomad4 SAS exome AF: 0.178

Gnomad4 FIN exome AF: 0.337

Gnomad4 NFE exome AF: 0.314

Gnomad4 OTH exome AF: 0.275

GnomAD4 genome AF: 0.262 AC: 39889 AN: 152080 Hom.: 5606 Cov.: 33 AF XY: 0.258 AC XY: 19211 AN XY: 74320

Gnomad4 AFR AF: 0.206

Gnomad4 AMR AF: 0.227

Gnomad4 ASJ AF: 0.312

Gnomad4 EAS AF: 0.0732

Gnomad4 SAS AF: 0.182

Gnomad4 FIN AF: 0.323

Gnomad4 NFE AF: 0.312

Gnomad4 OTH AF: 0.254

Alfa AF: 0.291 Hom.: 1146

Bravo AF: 0.248

Asia WGS AF: 0.137 AC: 478 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.86
DANN	Benign	0.60

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

Other links and lift over

dbSNP: rs12937300; hg19: chr17-18233810; COSMIC: COSV57398148; COSMIC: COSV57398148;