17-18337432-C-G

Variant names:

• chr17-18337432-C-G
• rs2168781
• NM_004169.5:c.815-1757G>C

Variant summary

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

The NM_004169.5(SHMT1):​c.815-1757G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.494 in 151,994 control chromosomes in the GnomAD database, including 19,926 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 0.49 (19926 hom., cov: 31)
• Consequence: SHMT1 NM_004169.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04
• Publications: 24 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.687 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHMT1	NM_004169.5	c.815-1757G>C		intron_variant	Intron 7 of 11	ENST00000316694.8	NP_004160.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SHMT1	ENST00000316694.8	c.815-1757G>C		intron_variant	Intron 7 of 11	1	NM_004169.5	ENSP00000318868.3

Frequencies

GnomAD3 genomes AF: 0.494 AC: 75064 AN: 151876 Hom.: 19893 Cov.: 31

Gnomad AFR AF: 0.694

Gnomad AMI AF: 0.390

Gnomad AMR AF: 0.451

Gnomad ASJ AF: 0.435

Gnomad EAS AF: 0.236

Gnomad SAS AF: 0.393

Gnomad FIN AF: 0.420

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.426

Gnomad OTH AF: 0.480

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

GnomAD4 genome AF: 0.494 AC: 75152 AN: 151994 Hom.: 19926 Cov.: 31 AF XY: 0.491 AC XY: 36501 AN XY: 74286

African (AFR) AF: 0.694 AC: 28782 AN: 41468

American (AMR) AF: 0.451 AC: 6894 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.435 AC: 1508 AN: 3464

East Asian (EAS) AF: 0.236 AC: 1214 AN: 5144

South Asian (SAS) AF: 0.393 AC: 1890 AN: 4812

European-Finnish (FIN) AF: 0.420 AC: 4438 AN: 10566

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.426 AC: 28929 AN: 67930

Other (OTH) AF: 0.481 AC: 1014 AN: 2110

Alfa AF: 0.488 Hom.: 2341

Bravo AF: 0.498

Asia WGS AF: 0.340 AC: 1185 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.88
DANN	Benign	0.45
PhyloP100		-1.0
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: rs2168781; hg19: chr17-18240746; COSMIC: COSV57398176; COSMIC: COSV57398176;