17-18328684-G-A

Variant names:

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

Variant summary

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

The ENST00000395684.5(SHMT1):​n.1841C>T 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 0.322 in 1,526,132 control chromosomes in the GnomAD database, including 84,979 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 0.39 (13197 hom., cov: 33)
  • Exomes 𝑓: 0.31 (71782 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.608 is higher than 0.05.

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>T		3_prime_UTR	Exon 12 of 12	NP_004160.3
	SHMT1	NM_148918.3		c.*66C>T		3_prime_UTR	Exon 11 of 11	NP_683718.1
	SHMT1	NM_001281786.2		c.*66C>T		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>T		non_coding_transcript_exon	Exon 7 of 7
	SHMT1	ENST00000316694.8	TSL:1 MANE Select	c.*66C>T		3_prime_UTR	Exon 12 of 12	ENSP00000318868.3
	SHMT1	ENST00000583780.2	TSL:1	c.*66C>T		3_prime_UTR	Exon 13 of 13	ENSP00000462041.2

Frequencies

GnomAD3 genomes AF: 0.388 AC: 58965 AN: 151948 Hom.: 13160 Cov.: 33

Gnomad AFR AF: 0.614

Gnomad AMI AF: 0.320

Gnomad AMR AF: 0.291

Gnomad ASJ AF: 0.361

Gnomad EAS AF: 0.0774

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.324

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.323

Gnomad OTH AF: 0.368

GnomAD4 exome AF: 0.315 AC: 432742 AN: 1374066 Hom.: 71782 Cov.: 26 AF XY: 0.310 AC XY: 210445 AN XY: 678660

African (AFR) AF: 0.619 AC: 19278 AN: 31136

American (AMR) AF: 0.266 AC: 9479 AN: 35670

Ashkenazi Jewish (ASJ) AF: 0.355 AC: 8897 AN: 25062

East Asian (EAS) AF: 0.0810 AC: 2886 AN: 35636

South Asian (SAS) AF: 0.194 AC: 15294 AN: 78776

European-Finnish (FIN) AF: 0.338 AC: 14920 AN: 44180

Middle Eastern (MID) AF: 0.331 AC: 1335 AN: 4030

European-Non Finnish (NFE) AF: 0.322 AC: 342198 AN: 1062356

Other (OTH) AF: 0.323 AC: 18455 AN: 57220

GnomAD4 genome AF: 0.388 AC: 59061 AN: 152066 Hom.: 13197 Cov.: 33 AF XY: 0.382 AC XY: 28359 AN XY: 74324

African (AFR) AF: 0.614 AC: 25472 AN: 41478

American (AMR) AF: 0.290 AC: 4433 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.361 AC: 1250 AN: 3464

East Asian (EAS) AF: 0.0780 AC: 404 AN: 5180

South Asian (SAS) AF: 0.198 AC: 957 AN: 4826

European-Finnish (FIN) AF: 0.324 AC: 3426 AN: 10564

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.323 AC: 21941 AN: 67972

Other (OTH) AF: 0.369 AC: 778 AN: 2110

Alfa AF: 0.322 Hom.: 6880

Bravo AF: 0.393

Asia WGS AF: 0.191 AC: 667 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.1
DANN	Benign	0.41
PhyloP100		-0.33
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs1979276; hg19: chr17-18231998; COSMIC: COSV57398119; COSMIC: COSV57398119;