17-18363661-G-C

Variant names:

• chr17-18363661-G-C
• rs638416
• NM_004169.5:c.-309C>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.-309C>G variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.665 in 152,246 control chromosomes in the GnomAD database, including 34,005 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 0.66 (33990 hom., cov: 35)
  • Exomes 𝑓: 0.72 (15 hom.)
• Consequence: SHMT1 NM_004169.5 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.02
• Publications: 11 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.747 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHMT1	NM_004169.5	c.-309C>G		upstream_gene_variant		ENST00000316694.8	NP_004160.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SHMT1	ENST00000316694.8	c.-309C>G		upstream_gene_variant		1	NM_004169.5	ENSP00000318868.3

Frequencies

GnomAD3 genomes AF: 0.664 AC: 101044 AN: 152070 Hom.: 33944 Cov.: 35

Gnomad AFR AF: 0.754

Gnomad AMI AF: 0.518

Gnomad AMR AF: 0.660

Gnomad ASJ AF: 0.676

Gnomad EAS AF: 0.534

Gnomad SAS AF: 0.522

Gnomad FIN AF: 0.652

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.635

Gnomad OTH AF: 0.657

GnomAD4 exome AF: 0.724 AC: 42 AN: 58 Hom.: 15 AF XY: 0.729 AC XY: 35 AN XY: 48

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 1.00 AC: 2 AN: 2

South Asian (SAS) AF: 0.500 AC: 1 AN: 2

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.700 AC: 35 AN: 50

Other (OTH) AF: 1.00 AC: 4 AN: 4

GnomAD4 genome AF: 0.665 AC: 101157 AN: 152188 Hom.: 33990 Cov.: 35 AF XY: 0.661 AC XY: 49211 AN XY: 74396

African (AFR) AF: 0.754 AC: 31343 AN: 41546

American (AMR) AF: 0.660 AC: 10087 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.676 AC: 2345 AN: 3470

East Asian (EAS) AF: 0.535 AC: 2760 AN: 5162

South Asian (SAS) AF: 0.523 AC: 2525 AN: 4828

European-Finnish (FIN) AF: 0.652 AC: 6905 AN: 10598

Middle Eastern (MID) AF: 0.602 AC: 177 AN: 294

European-Non Finnish (NFE) AF: 0.635 AC: 43160 AN: 67982

Other (OTH) AF: 0.655 AC: 1385 AN: 2114

Alfa AF: 0.659 Hom.: 4126

Bravo AF: 0.668

Asia WGS AF: 0.511 AC: 1780 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.14
DANN	Benign	0.29
PhyloP100		-4.0
PromoterAI		-0.089	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs638416; hg19: chr17-18266975;