rs11868708

Variant names:

• chr17-18341299-T-A
• rs11868708
• NM_004169.5:c.520-486A>T

Your query was ambiguous. Multiple possible variants found:

• chr17-18341299-T-A
• chr17-18341299-T-C
• chr17-18341299-T-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004169.5(SHMT1):​c.520-486A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SHMT1 NM_004169.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.265
• Publications: 12 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHMT1	NM_004169.5	MANE Select	c.520-486A>T		intron	N/A	NP_004160.3
	SHMT1	NM_148918.3		c.520-486A>T		intron	N/A	NP_683718.1	P34896-2
	SHMT1	NM_001281786.2		c.106-486A>T		intron	N/A	NP_001268715.1	P34896-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHMT1	ENST00000316694.8	TSL:1 MANE Select	c.520-486A>T		intron	N/A	ENSP00000318868.3	P34896-1
	SHMT1	ENST00000583780.2	TSL:1	c.520-486A>T		intron	N/A	ENSP00000462041.2	P34896-1
	SHMT1	ENST00000354098.7	TSL:1	c.520-486A>T		intron	N/A	ENSP00000318805.3	P34896-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 37110 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 19200

African (AFR) AF: 0.00 AC: 0 AN: 660

American (AMR) AF: 0.00 AC: 0 AN: 3264

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 698

East Asian (EAS) AF: 0.00 AC: 0 AN: 1966

South Asian (SAS) AF: 0.00 AC: 0 AN: 5146

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 104

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 21644

Other (OTH) AF: 0.00 AC: 0 AN: 2006

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 89

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.9
DANN	Benign	0.50
PhyloP100		-0.27

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: rs11868708; hg19: chr17-18244613;