rs9910090

Variant names:

• chr17-18347085-A-C
• rs9910090
• NM_004169.5:c.519+411T>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+411T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 152,118 control chromosomes in the GnomAD database, including 5,248 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 (5248 hom., cov: 33)
• Consequence: SHMT1 NM_004169.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.280
• Publications: 5 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.288 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHMT1	NM_004169.5	c.519+411T>G		intron_variant	Intron 5 of 11	ENST00000316694.8	NP_004160.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SHMT1	ENST00000316694.8	c.519+411T>G		intron_variant	Intron 5 of 11	1	NM_004169.5	ENSP00000318868.3

Frequencies

GnomAD3 genomes AF: 0.260 AC: 39527 AN: 152000 Hom.: 5233 Cov.: 33

Gnomad AFR AF: 0.272

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.266

Gnomad ASJ AF: 0.299

Gnomad EAS AF: 0.300

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.275

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.249

Gnomad OTH AF: 0.268

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

GnomAD4 genome AF: 0.260 AC: 39584 AN: 152118 Hom.: 5248 Cov.: 33 AF XY: 0.258 AC XY: 19224 AN XY: 74370

African (AFR) AF: 0.272 AC: 11295 AN: 41486

American (AMR) AF: 0.266 AC: 4064 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.299 AC: 1039 AN: 3472

East Asian (EAS) AF: 0.300 AC: 1555 AN: 5176

South Asian (SAS) AF: 0.203 AC: 981 AN: 4830

European-Finnish (FIN) AF: 0.275 AC: 2905 AN: 10578

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.249 AC: 16946 AN: 67982

Other (OTH) AF: 0.269 AC: 567 AN: 2106

Alfa AF: 0.253 Hom.: 1915

Bravo AF: 0.267

Asia WGS AF: 0.240 AC: 832 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.4
DANN	Benign	0.70
PhyloP100		-0.28
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: rs9910090; hg19: chr17-18250399;