rs12952556

Positions:

• chr17-18328483-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.*267A>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 0.284 in 496,084 control chromosomes in the GnomAD database, including 21,454 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 0.31 (7577 hom., cov: 33)
  • Exomes 𝑓: 0.27 (13877 hom.)
• Consequence: SHMT1 NM_004169.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.96

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 (AFR) allele frequency at 95% confidence interval = 0.35 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SHMT1	NM_004169.5	c.*267A>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.*267A>G		3_prime_UTR_variant	12/12	1	NM_004169.5	ENSP00000318868	P1

Frequencies

GnomAD3 genomes AF: 0.308 AC: 46855 AN: 152028 Hom.: 7574 Cov.: 33

Gnomad AFR AF: 0.355

Gnomad AMI AF: 0.319

Gnomad AMR AF: 0.249

Gnomad ASJ AF: 0.327

Gnomad EAS AF: 0.0732

Gnomad SAS AF: 0.186

Gnomad FIN AF: 0.325

Gnomad MID AF: 0.306

Gnomad NFE AF: 0.316

Gnomad OTH AF: 0.295

GnomAD4 exome AF: 0.273 AC: 93805 AN: 343938 Hom.: 13877 Cov.: 3 AF XY: 0.266 AC XY: 48321 AN XY: 181488

Gnomad4 AFR exome AF: 0.339

Gnomad4 AMR exome AF: 0.234

Gnomad4 ASJ exome AF: 0.318

Gnomad4 EAS exome AF: 0.0756

Gnomad4 SAS exome AF: 0.181

Gnomad4 FIN exome AF: 0.326

Gnomad4 NFE exome AF: 0.304

Gnomad4 OTH exome AF: 0.281

GnomAD4 genome AF: 0.308 AC: 46895 AN: 152146 Hom.: 7577 Cov.: 33 AF XY: 0.303 AC XY: 22567 AN XY: 74370

Gnomad4 AFR AF: 0.355

Gnomad4 AMR AF: 0.249

Gnomad4 ASJ AF: 0.327

Gnomad4 EAS AF: 0.0738

Gnomad4 SAS AF: 0.187

Gnomad4 FIN AF: 0.325

Gnomad4 NFE AF: 0.316

Gnomad4 OTH AF: 0.292

Alfa AF: 0.310 Hom.: 6496

Bravo AF: 0.300

Asia WGS AF: 0.152 AC: 532 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	8.8
DANN	Benign	0.58
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.0

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: rs12952556; hg19: chr17-18231797; COSMIC: COSV57398111; COSMIC: COSV57398111;