17-18328684-G-C

Variant names:

• chr17-18328684-G-C
• rs1979276
• ENST00000395684.5:n.1841C>G

Variant summary

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

The ENST00000395684.5(SHMT1):​n.1841C>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000419 in 1,527,976 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000039 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000042 (0 hom.)
• Consequence: SHMT1 ENST00000395684.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.326
• Publications: 31 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=-0.83).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000395684.5. 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.*66C>G		3_prime_UTR	Exon 12 of 12	NP_004160.3
	SHMT1	NM_148918.3		c.*66C>G		3_prime_UTR	Exon 11 of 11	NP_683718.1
	SHMT1	NM_001281786.2		c.*66C>G		3_prime_UTR	Exon 11 of 11	NP_001268715.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHMT1	ENST00000395684.5	TSL:1	n.1841C>G		non_coding_transcript_exon	Exon 7 of 7
	SHMT1	ENST00000316694.8	TSL:1 MANE Select	c.*66C>G		3_prime_UTR	Exon 12 of 12	ENSP00000318868.3
	SHMT1	ENST00000583780.2	TSL:1	c.*66C>G		3_prime_UTR	Exon 13 of 13	ENSP00000462041.2

Frequencies

GnomAD3 genomes AF: 0.0000395 AC: 6 AN: 152010 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000422 AC: 58 AN: 1375966 Hom.: 0 Cov.: 26 AF XY: 0.0000368 AC XY: 25 AN XY: 679562

African (AFR) AF: 0.00 AC: 0 AN: 31178

American (AMR) AF: 0.0000280 AC: 1 AN: 35684

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25082

East Asian (EAS) AF: 0.00 AC: 0 AN: 35648

South Asian (SAS) AF: 0.00 AC: 0 AN: 78806

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44248

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4036

European-Non Finnish (NFE) AF: 0.0000536 AC: 57 AN: 1063988

Other (OTH) AF: 0.00 AC: 0 AN: 57296

GnomAD4 genome AF: 0.0000395 AC: 6 AN: 152010 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74234

African (AFR) AF: 0.0000242 AC: 1 AN: 41374

American (AMR) AF: 0.00 AC: 0 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10578

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 67996

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 6880

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.86
DANN	Benign	0.40
PhyloP100		-0.33
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs1979276; hg19: chr17-18231998;