17-18341299-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.520-486A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 188,942 control chromosomes in the GnomAD database, including 4,973 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 (3883 hom., cov: 32)
  • Exomes 𝑓: 0.23 (1090 hom.)
• Consequence: SHMT1 NM_004169.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.265

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.284 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SHMT1	NM_004169.5	c.520-486A>G		intron_variant		ENST00000316694.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SHMT1	ENST00000316694.8	c.520-486A>G		intron_variant		1	NM_004169.5	P1

Frequencies

GnomAD3 genomes AF: 0.220 AC: 33441 AN: 151794 Hom.: 3877 Cov.: 32

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.239

Gnomad ASJ AF: 0.264

Gnomad EAS AF: 0.296

Gnomad SAS AF: 0.180

Gnomad FIN AF: 0.277

Gnomad MID AF: 0.207

Gnomad NFE AF: 0.244

Gnomad OTH AF: 0.226

GnomAD4 exome AF: 0.229 AC: 8481 AN: 37030 Hom.: 1090 Cov.: 0 AF XY: 0.225 AC XY: 4306 AN XY: 19160

Gnomad4 AFR exome AF: 0.144

Gnomad4 AMR exome AF: 0.239

Gnomad4 ASJ exome AF: 0.248

Gnomad4 EAS exome AF: 0.293

Gnomad4 SAS exome AF: 0.190

Gnomad4 FIN exome AF: 0.265

Gnomad4 NFE exome AF: 0.230

Gnomad4 OTH exome AF: 0.232

GnomAD4 genome AF: 0.220 AC: 33465 AN: 151912 Hom.: 3883 Cov.: 32 AF XY: 0.220 AC XY: 16313 AN XY: 74224

Gnomad4 AFR AF: 0.152

Gnomad4 AMR AF: 0.239

Gnomad4 ASJ AF: 0.264

Gnomad4 EAS AF: 0.296

Gnomad4 SAS AF: 0.181

Gnomad4 FIN AF: 0.277

Gnomad4 NFE AF: 0.244

Gnomad4 OTH AF: 0.223

Alfa AF: 0.0694 Hom.: 79

Bravo AF: 0.220

Asia WGS AF: 0.202 AC: 700 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	5.3
Dann	Benign	0.38

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: rs11868708; hg19: chr17-18244613;