rs3783

Variant names:

• chr17-18328703-G-C
• rs3783
• NM_004169.5:c.*47C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004169.5(SHMT1):​c.*47C>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 0.291 in 1,545,742 control chromosomes in the GnomAD database, including 68,375 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 0.26 (5595 hom., cov: 32)
  • Exomes 𝑓: 0.29 (62780 hom.)
• Consequence: SHMT1 NM_004169.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15
• Publications: 21 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.309 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004169.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHMT1	NM_004169.5	MANE Select	c.*47C>G		3_prime_UTR	Exon 12 of 12	NP_004160.3
	SHMT1	NM_148918.3		c.*47C>G		3_prime_UTR	Exon 11 of 11	NP_683718.1	P34896-2
	SHMT1	NM_001281786.2		c.*47C>G		3_prime_UTR	Exon 11 of 11	NP_001268715.1	P34896-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHMT1	ENST00000316694.8	TSL:1 MANE Select	c.*47C>G		3_prime_UTR	Exon 12 of 12	ENSP00000318868.3	P34896-1
	SHMT1	ENST00000583780.2	TSL:1	c.*47C>G		3_prime_UTR	Exon 13 of 13	ENSP00000462041.2	P34896-1
	SHMT1	ENST00000354098.7	TSL:1	c.*47C>G		3_prime_UTR	Exon 11 of 11	ENSP00000318805.3	P34896-2

Frequencies

GnomAD3 genomes AF: 0.262 AC: 39892 AN: 152024 Hom.: 5596 Cov.: 32

Gnomad AFR AF: 0.206

Gnomad AMI AF: 0.320

Gnomad AMR AF: 0.227

Gnomad ASJ AF: 0.314

Gnomad EAS AF: 0.0739

Gnomad SAS AF: 0.182

Gnomad FIN AF: 0.323

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.312

Gnomad OTH AF: 0.259

GnomAD2 exomes AF: 0.254 AC: 38669 AN: 152280 AF XY: 0.252

Gnomad AFR exome AF: 0.197

Gnomad AMR exome AF: 0.224

Gnomad ASJ exome AF: 0.322

Gnomad EAS exome AF: 0.0728

Gnomad FIN exome AF: 0.338

Gnomad NFE exome AF: 0.306

Gnomad OTH exome AF: 0.266

GnomAD4 exome AF: 0.294 AC: 410382 AN: 1393600 Hom.: 62780 Cov.: 31 AF XY: 0.291 AC XY: 199887 AN XY: 687528

African (AFR) AF: 0.204 AC: 6423 AN: 31534

American (AMR) AF: 0.222 AC: 7923 AN: 35740

Ashkenazi Jewish (ASJ) AF: 0.312 AC: 7865 AN: 25172

East Asian (EAS) AF: 0.0802 AC: 2865 AN: 35744

South Asian (SAS) AF: 0.179 AC: 14225 AN: 79298

European-Finnish (FIN) AF: 0.337 AC: 15720 AN: 46592

Middle Eastern (MID) AF: 0.232 AC: 947 AN: 4074

European-Non Finnish (NFE) AF: 0.314 AC: 338468 AN: 1077676

Other (OTH) AF: 0.276 AC: 15946 AN: 57770

GnomAD4 genome AF: 0.262 AC: 39902 AN: 152142 Hom.: 5595 Cov.: 32 AF XY: 0.259 AC XY: 19233 AN XY: 74362

African (AFR) AF: 0.206 AC: 8539 AN: 41522

American (AMR) AF: 0.227 AC: 3466 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.314 AC: 1089 AN: 3470

East Asian (EAS) AF: 0.0745 AC: 386 AN: 5182

South Asian (SAS) AF: 0.183 AC: 881 AN: 4824

European-Finnish (FIN) AF: 0.323 AC: 3417 AN: 10584

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.312 AC: 21225 AN: 67978

Other (OTH) AF: 0.256 AC: 540 AN: 2108

Alfa AF: 0.300 Hom.: 1457

Bravo AF: 0.248

Asia WGS AF: 0.137 AC: 477 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.3
DANN	Benign	0.68
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3783; hg19: chr17-18232017; COSMIC: COSV57398124; COSMIC: COSV57398124;