rs12952556

Variant names:

• chr17-18328483-T-C
• rs12952556
• ENST00000395684.5:n.2042A>G

Variant summary

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

The ENST00000316694.8(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 ENST00000316694.8 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.96
• 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 (AFR) allele frequency at 95% confidence interval = 0.35 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000316694.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHMT1	NM_004169.5	MANE Select	c.*267A>G		3_prime_UTR	Exon 12 of 12	NP_004160.3
	SHMT1	NM_148918.3		c.*267A>G		3_prime_UTR	Exon 11 of 11	NP_683718.1
	SHMT1	NM_001281786.2		c.*267A>G		3_prime_UTR	Exon 11 of 11	NP_001268715.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHMT1	ENST00000395684.5	TSL:1	n.2042A>G		non_coding_transcript_exon	Exon 7 of 7
	SHMT1	ENST00000316694.8	TSL:1 MANE Select	c.*267A>G		3_prime_UTR	Exon 12 of 12	ENSP00000318868.3
	SHMT1	ENST00000583780.2	TSL:1	c.*267A>G		3_prime_UTR	Exon 13 of 13	ENSP00000462041.2

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

African (AFR) AF: 0.339 AC: 3419 AN: 10084

American (AMR) AF: 0.234 AC: 3478 AN: 14874

Ashkenazi Jewish (ASJ) AF: 0.318 AC: 3373 AN: 10606

East Asian (EAS) AF: 0.0756 AC: 1663 AN: 22002

South Asian (SAS) AF: 0.181 AC: 7582 AN: 41882

European-Finnish (FIN) AF: 0.326 AC: 5958 AN: 18282

Middle Eastern (MID) AF: 0.254 AC: 369 AN: 1452

European-Non Finnish (NFE) AF: 0.304 AC: 62418 AN: 205054

Other (OTH) AF: 0.281 AC: 5545 AN: 19702

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

African (AFR) AF: 0.355 AC: 14738 AN: 41484

American (AMR) AF: 0.249 AC: 3803 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.327 AC: 1136 AN: 3472

East Asian (EAS) AF: 0.0738 AC: 382 AN: 5178

South Asian (SAS) AF: 0.187 AC: 903 AN: 4830

European-Finnish (FIN) AF: 0.325 AC: 3441 AN: 10578

Middle Eastern (MID) AF: 0.298 AC: 87 AN: 292

European-Non Finnish (NFE) AF: 0.316 AC: 21497 AN: 67998

Other (OTH) AF: 0.292 AC: 617 AN: 2110

Alfa AF: 0.311 Hom.: 8634

Bravo AF: 0.300

Asia WGS AF: 0.152 AC: 532 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	8.8
DANN	Benign	0.58
PhyloP100		2.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.0
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: rs12952556; hg19: chr17-18231797; COSMIC: COSV57398111; COSMIC: COSV57398111;