rs2273029

Positions:

• chr17-18333025-G-A

Variant summary

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

The NM_004169.5(SHMT1):​c.1054+141C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 1,087,362 control chromosomes in the GnomAD database, including 30,478 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 0.22 (3856 hom., cov: 33)
  • Exomes 𝑓: 0.24 (26622 hom.)
• Consequence: SHMT1 NM_004169.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.678

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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.285 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SHMT1	NM_004169.5	c.1054+141C>T		intron_variant		ENST00000316694.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SHMT1	ENST00000316694.8	c.1054+141C>T		intron_variant		1	NM_004169.5	P1

Frequencies

GnomAD3 genomes AF: 0.219 AC: 33336 AN: 152122 Hom.: 3850 Cov.: 33

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.238

Gnomad ASJ AF: 0.260

Gnomad EAS AF: 0.297

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.275

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.242

Gnomad OTH AF: 0.225

GnomAD3 exomes AF: 0.238 AC: 42390 AN: 178122 Hom.: 5142 AF XY: 0.237 AC XY: 22860 AN XY: 96580

Gnomad AFR exome AF: 0.146

Gnomad AMR exome AF: 0.245

Gnomad ASJ exome AF: 0.261

Gnomad EAS exome AF: 0.308

Gnomad SAS exome AF: 0.189

Gnomad FIN exome AF: 0.267

Gnomad NFE exome AF: 0.245

Gnomad OTH exome AF: 0.247

GnomAD4 exome AF: 0.236 AC: 220722 AN: 935122 Hom.: 26622 Cov.: 12 AF XY: 0.235 AC XY: 113128 AN XY: 482062

Gnomad4 AFR exome AF: 0.152

Gnomad4 AMR exome AF: 0.248

Gnomad4 ASJ exome AF: 0.268

Gnomad4 EAS exome AF: 0.247

Gnomad4 SAS exome AF: 0.193

Gnomad4 FIN exome AF: 0.262

Gnomad4 NFE exome AF: 0.239

Gnomad4 OTH exome AF: 0.238

GnomAD4 genome AF: 0.219 AC: 33360 AN: 152240 Hom.: 3856 Cov.: 33 AF XY: 0.218 AC XY: 16255 AN XY: 74418

Gnomad4 AFR AF: 0.152

Gnomad4 AMR AF: 0.239

Gnomad4 ASJ AF: 0.260

Gnomad4 EAS AF: 0.297

Gnomad4 SAS AF: 0.180

Gnomad4 FIN AF: 0.275

Gnomad4 NFE AF: 0.243

Gnomad4 OTH AF: 0.223

Alfa AF: 0.230 Hom.: 773

Bravo AF: 0.220

Asia WGS AF: 0.199 AC: 693 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	7.5
DANN	Benign	0.66

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: rs2273029; hg19: chr17-18236339; COSMIC: COSV57397540; COSMIC: COSV57397540;