rs9910090

chr17-18347085-A-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
SHMT1	NM_004169.5	c.519+411T>G		intron_variant		ENST00000316694.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SHMT1	ENST00000316694.8	c.519+411T>G		intron_variant		1	NM_004169.5	P1

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

Gnomad4 AFR AF: 0.272

Gnomad4 AMR AF: 0.266

Gnomad4 ASJ AF: 0.299

Gnomad4 EAS AF: 0.300

Gnomad4 SAS AF: 0.203

Gnomad4 FIN AF: 0.275

Gnomad4 NFE AF: 0.249

Gnomad4 OTH AF: 0.269

Alfa AF: 0.251 Hom.: 1507

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs9910090; hg19: chr17-18250399;