rs1979276

Positions:

• chr17-18328684-G-A
• chr17-18328684-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.*66C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.322 in 1,526,132 control chromosomes in the GnomAD database, including 84,979 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 0.39 (13197 hom., cov: 33)
  • Exomes 𝑓: 0.31 (71782 hom.)
• Consequence: SHMT1 NM_004169.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.326

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.608 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SHMT1	NM_004169.5	c.*66C>T		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.*66C>T		3_prime_UTR_variant	12/12	1	NM_004169.5	ENSP00000318868	P1

Frequencies

GnomAD3 genomes AF: 0.388 AC: 58965 AN: 151948 Hom.: 13160 Cov.: 33

Gnomad AFR AF: 0.614

Gnomad AMI AF: 0.320

Gnomad AMR AF: 0.291

Gnomad ASJ AF: 0.361

Gnomad EAS AF: 0.0774

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.324

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.323

Gnomad OTH AF: 0.368

GnomAD4 exome AF: 0.315 AC: 432742 AN: 1374066 Hom.: 71782 Cov.: 26 AF XY: 0.310 AC XY: 210445 AN XY: 678660

Gnomad4 AFR exome AF: 0.619

Gnomad4 AMR exome AF: 0.266

Gnomad4 ASJ exome AF: 0.355

Gnomad4 EAS exome AF: 0.0810

Gnomad4 SAS exome AF: 0.194

Gnomad4 FIN exome AF: 0.338

Gnomad4 NFE exome AF: 0.322

Gnomad4 OTH exome AF: 0.323

GnomAD4 genome AF: 0.388 AC: 59061 AN: 152066 Hom.: 13197 Cov.: 33 AF XY: 0.382 AC XY: 28359 AN XY: 74324

Gnomad4 AFR AF: 0.614

Gnomad4 AMR AF: 0.290

Gnomad4 ASJ AF: 0.361

Gnomad4 EAS AF: 0.0780

Gnomad4 SAS AF: 0.198

Gnomad4 FIN AF: 0.324

Gnomad4 NFE AF: 0.323

Gnomad4 OTH AF: 0.369

Alfa AF: 0.314 Hom.: 5230

Bravo AF: 0.393

Asia WGS AF: 0.191 AC: 667 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.1
DANN	Benign	0.41
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs1979276; hg19: chr17-18231998; COSMIC: COSV57398119; COSMIC: COSV57398119;