Genetic Variant SHMT1:n.357A>G (chr17-18341299-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000395684.5(SHMT1):n.357A>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 0.222 in 188,942 control chromosomes in the GnomAD database, including 4,973 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 0.22 ( 3883 hom., cov: 32)

Exomes 𝑓: 0.23 ( 1090 hom. )

Consequence

SHMT1
ENST00000395684.5 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.265

Publications

12 publications found

Variant links:

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]

SHMT1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.284 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHMT1	NM_004169.5 link	c.520-486A>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 link	c.520-486A>G		intron_variant	Intron 5 of 11	1	NM_004169.5	ENSP00000318868.3

Frequencies

GnomAD3 genomes

AF:

0.220

AC:

33441

AN:

151794

Hom.:

3877

Cov.:

show subpopulations

Gnomad AFR

AF:

0.152

Gnomad AMI

AF:

0.164

Gnomad AMR

AF:

0.239

Gnomad ASJ

AF:

0.264

Gnomad EAS

AF:

0.296

Gnomad SAS

AF:

0.180

Gnomad FIN

AF:

0.277

Gnomad MID

AF:

0.207

Gnomad NFE

AF:

0.244

Gnomad OTH

AF:

0.226

GnomAD4 exome

AF:

0.229

AC:

8481

AN:

37030

Hom.:

1090

Cov.:

AF XY:

0.225

AC XY:

4306

AN XY:

19160

show subpopulations

African (AFR)

AF:

0.144

AC:

AN:

660

American (AMR)

AF:

0.239

AC:

779

AN:

3258

Ashkenazi Jewish (ASJ)

AF:

0.248

AC:

173

AN:

698

East Asian (EAS)

AF:

0.293

AC:

574

AN:

1958

South Asian (SAS)

AF:

0.190

AC:

975

AN:

5136

European-Finnish (FIN)

AF:

0.265

AC:

430

AN:

1620

Middle Eastern (MID)

AF:

0.288

AC:

AN:

104

European-Non Finnish (NFE)

AF:

0.230

AC:

4960

AN:

21594

Other (OTH)

AF:

0.232

AC:

465

AN:

2002

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

317

633

950

1266

1583

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

148

222

296

370

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.220

AC:

33465

AN:

151912

Hom.:

3883

Cov.:

AF XY:

0.220

AC XY:

16313

AN XY:

74224

show subpopulations

African (AFR)

AF:

0.152

AC:

6315

AN:

41432

American (AMR)

AF:

0.239

AC:

3654

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.264

AC:

915

AN:

3470

East Asian (EAS)

AF:

0.296

AC:

1531

AN:

5168

South Asian (SAS)

AF:

0.181

AC:

871

AN:

4800

European-Finnish (FIN)

AF:

0.277

AC:

2910

AN:

10524

Middle Eastern (MID)

AF:

0.199

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.244

AC:

16590

AN:

67948

Other (OTH)

AF:

0.223

AC:

471

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1331

2662

3994

5325

6656

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

364

728

1092

1456

1820

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0747

Hom.:

Bravo

AF:

0.220

Asia WGS

AF:

0.202

AC:

700

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

5.3

(source)

DANN

Benign

0.38

PhyloP100

-0.27

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over