rs7207306

Positions:

• chr17-18344048-C-T

Variant summary

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

The NM_004169.5(SHMT1):​c.520-3235G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.298 in 151,810 control chromosomes in the GnomAD database, including 7,105 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 0.30 (7105 hom., cov: 30)
• Consequence: SHMT1 NM_004169.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.241

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 (AFR) allele frequency at 95% confidence interval = 0.343 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SHMT1	NM_004169.5	c.520-3235G>A		intron_variant		ENST00000316694.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SHMT1	ENST00000316694.8	c.520-3235G>A		intron_variant		1	NM_004169.5	P1

Frequencies

GnomAD3 genomes AF: 0.298 AC: 45280 AN: 151692 Hom.: 7104 Cov.: 30

Gnomad AFR AF: 0.348

Gnomad AMI AF: 0.319

Gnomad AMR AF: 0.242

Gnomad ASJ AF: 0.317

Gnomad EAS AF: 0.0719

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.289

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.308

Gnomad OTH AF: 0.283

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.298 AC: 45311 AN: 151810 Hom.: 7105 Cov.: 30 AF XY: 0.292 AC XY: 21690 AN XY: 74188

Gnomad4 AFR AF: 0.348

Gnomad4 AMR AF: 0.241

Gnomad4 ASJ AF: 0.317

Gnomad4 EAS AF: 0.0725

Gnomad4 SAS AF: 0.178

Gnomad4 FIN AF: 0.289

Gnomad4 NFE AF: 0.308

Gnomad4 OTH AF: 0.280

Alfa AF: 0.316 Hom.: 1224

Bravo AF: 0.293

Asia WGS AF: 0.134 AC: 470 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	1.1
DANN	Benign	0.29

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: rs7207306; hg19: chr17-18247362; COSMIC: COSV57398206; COSMIC: COSV57398206;