17-18344707-T-C

Variant names:

• chr17-18344707-T-C
• rs9909104
• NM_004169.5:c.519+2789A>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.519+2789A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 151,706 control chromosomes in the GnomAD database, including 7,302 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 0.30 (7302 hom., cov: 31)
• Consequence: SHMT1 NM_004169.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.723
• Publications: 22 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.404 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHMT1	NM_004169.5	MANE Select	c.519+2789A>G		intron	N/A	NP_004160.3
	SHMT1	NM_148918.3		c.519+2789A>G		intron	N/A	NP_683718.1
	SHMT1	NM_001281786.2		c.105+2789A>G		intron	N/A	NP_001268715.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHMT1	ENST00000316694.8	TSL:1 MANE Select	c.519+2789A>G		intron	N/A	ENSP00000318868.3
	SHMT1	ENST00000583780.2	TSL:1	c.519+2789A>G		intron	N/A	ENSP00000462041.2
	SHMT1	ENST00000354098.7	TSL:1	c.519+2789A>G		intron	N/A	ENSP00000318805.3

Frequencies

GnomAD3 genomes AF: 0.301 AC: 45554 AN: 151590 Hom.: 7281 Cov.: 31

Gnomad AFR AF: 0.409

Gnomad AMI AF: 0.165

Gnomad AMR AF: 0.283

Gnomad ASJ AF: 0.302

Gnomad EAS AF: 0.301

Gnomad SAS AF: 0.202

Gnomad FIN AF: 0.274

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.252

Gnomad OTH AF: 0.299

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.301 AC: 45635 AN: 151706 Hom.: 7302 Cov.: 31 AF XY: 0.298 AC XY: 22089 AN XY: 74080

African (AFR) AF: 0.409 AC: 16906 AN: 41336

American (AMR) AF: 0.283 AC: 4311 AN: 15212

Ashkenazi Jewish (ASJ) AF: 0.302 AC: 1049 AN: 3468

East Asian (EAS) AF: 0.301 AC: 1553 AN: 5156

South Asian (SAS) AF: 0.204 AC: 979 AN: 4810

European-Finnish (FIN) AF: 0.274 AC: 2873 AN: 10486

Middle Eastern (MID) AF: 0.281 AC: 82 AN: 292

European-Non Finnish (NFE) AF: 0.252 AC: 17099 AN: 67930

Other (OTH) AF: 0.301 AC: 633 AN: 2106

Alfa AF: 0.274 Hom.: 8835

Bravo AF: 0.313

Asia WGS AF: 0.245 AC: 851 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	5.0
DANN	Benign	0.84
PhyloP100		-0.72
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: rs9909104; hg19: chr17-18248021;