rs3783

Positions:

• chr17-18328703-G-C

Variant summary

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

The NM_004169.5(SHMT1):​c.*47C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 1,545,742 control chromosomes in the GnomAD database, including 68,375 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 (5595 hom., cov: 32)
  • Exomes 𝑓: 0.29 (62780 hom.)
• Consequence: SHMT1 NM_004169.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15

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=-0.82).
• 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	Protein	UniProt
SHMT1	NM_004169.5	c.*47C>G		3_prime_UTR_variant	12/12	ENST00000316694.8	NP_004160.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SHMT1	ENST00000316694.8	c.*47C>G		3_prime_UTR_variant	12/12	1	NM_004169.5	ENSP00000318868	P1

Frequencies

GnomAD3 genomes AF: 0.262 AC: 39892 AN: 152024 Hom.: 5596 Cov.: 32

Gnomad AFR AF: 0.206

Gnomad AMI AF: 0.320

Gnomad AMR AF: 0.227

Gnomad ASJ AF: 0.314

Gnomad EAS AF: 0.0739

Gnomad SAS AF: 0.182

Gnomad FIN AF: 0.323

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.312

Gnomad OTH AF: 0.259

GnomAD3 exomes AF: 0.254 AC: 38669 AN: 152280 Hom.: 5342 AF XY: 0.252 AC XY: 20399 AN XY: 80962

Gnomad AFR exome AF: 0.197

Gnomad AMR exome AF: 0.224

Gnomad ASJ exome AF: 0.322

Gnomad EAS exome AF: 0.0728

Gnomad SAS exome AF: 0.182

Gnomad FIN exome AF: 0.338

Gnomad NFE exome AF: 0.306

Gnomad OTH exome AF: 0.266

GnomAD4 exome AF: 0.294 AC: 410382 AN: 1393600 Hom.: 62780 Cov.: 31 AF XY: 0.291 AC XY: 199887 AN XY: 687528

Gnomad4 AFR exome AF: 0.204

Gnomad4 AMR exome AF: 0.222

Gnomad4 ASJ exome AF: 0.312

Gnomad4 EAS exome AF: 0.0802

Gnomad4 SAS exome AF: 0.179

Gnomad4 FIN exome AF: 0.337

Gnomad4 NFE exome AF: 0.314

Gnomad4 OTH exome AF: 0.276

GnomAD4 genome AF: 0.262 AC: 39902 AN: 152142 Hom.: 5595 Cov.: 32 AF XY: 0.259 AC XY: 19233 AN XY: 74362

Gnomad4 AFR AF: 0.206

Gnomad4 AMR AF: 0.227

Gnomad4 ASJ AF: 0.314

Gnomad4 EAS AF: 0.0745

Gnomad4 SAS AF: 0.183

Gnomad4 FIN AF: 0.323

Gnomad4 NFE AF: 0.312

Gnomad4 OTH AF: 0.256

Alfa AF: 0.300 Hom.: 1457

Bravo AF: 0.248

Asia WGS AF: 0.137 AC: 477 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.3
DANN	Benign	0.68

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: rs3783; hg19: chr17-18232017; COSMIC: COSV57398124; COSMIC: COSV57398124;