rs2273028

Positions:

• chr17-18335698-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.815-23C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.316 in 1,522,650 control chromosomes in the GnomAD database, including 80,193 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 0.36 (10871 hom., cov: 32)
  • Exomes 𝑓: 0.31 (69322 hom.)
• Consequence: SHMT1 NM_004169.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.390

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 (AFR) allele frequency at 95% confidence interval = 0.512 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SHMT1	NM_004169.5	c.815-23C>T		intron_variant		ENST00000316694.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SHMT1	ENST00000316694.8	c.815-23C>T		intron_variant		1	NM_004169.5	P1

Frequencies

GnomAD3 genomes AF: 0.361 AC: 54778 AN: 151882 Hom.: 10852 Cov.: 32

Gnomad AFR AF: 0.517

Gnomad AMI AF: 0.318

Gnomad AMR AF: 0.281

Gnomad ASJ AF: 0.358

Gnomad EAS AF: 0.0769

Gnomad SAS AF: 0.208

Gnomad FIN AF: 0.325

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.323

Gnomad OTH AF: 0.348

GnomAD3 exomes AF: 0.294 AC: 73951 AN: 251470 Hom.: 12033 AF XY: 0.288 AC XY: 39161 AN XY: 135914

Gnomad AFR exome AF: 0.518

Gnomad AMR exome AF: 0.257

Gnomad ASJ exome AF: 0.362

Gnomad EAS exome AF: 0.0770

Gnomad SAS exome AF: 0.204

Gnomad FIN exome AF: 0.337

Gnomad NFE exome AF: 0.317

Gnomad OTH exome AF: 0.320

GnomAD4 exome AF: 0.311 AC: 426193 AN: 1370650 Hom.: 69322 Cov.: 21 AF XY: 0.307 AC XY: 210720 AN XY: 687012

Gnomad4 AFR exome AF: 0.523

Gnomad4 AMR exome AF: 0.258

Gnomad4 ASJ exome AF: 0.354

Gnomad4 EAS exome AF: 0.0811

Gnomad4 SAS exome AF: 0.203

Gnomad4 FIN exome AF: 0.339

Gnomad4 NFE exome AF: 0.321

Gnomad4 OTH exome AF: 0.316

GnomAD4 genome AF: 0.361 AC: 54853 AN: 152000 Hom.: 10871 Cov.: 32 AF XY: 0.355 AC XY: 26393 AN XY: 74290

Gnomad4 AFR AF: 0.517

Gnomad4 AMR AF: 0.281

Gnomad4 ASJ AF: 0.358

Gnomad4 EAS AF: 0.0775

Gnomad4 SAS AF: 0.210

Gnomad4 FIN AF: 0.325

Gnomad4 NFE AF: 0.323

Gnomad4 OTH AF: 0.349

Alfa AF: 0.324 Hom.: 14521

Bravo AF: 0.361

Asia WGS AF: 0.187 AC: 654 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	0.54
DANN	Benign	0.42

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: rs2273028; hg19: chr17-18239012; COSMIC: COSV57398158; COSMIC: COSV57398158;