Genetic Variant ENST00000395684.5:n.1822C>G (chr17-18328703-G-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.1822C>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 0.291 in 1,545,742 control chromosomes in the GnomAD database, including 68,375 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 ( 5595 hom., cov: 32)

Exomes 𝑓: 0.29 ( 62780 hom. )

Consequence

SHMT1
ENST00000395684.5 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.15

Publications

21 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=-0.82).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.309 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHMT1	NM_004169.5 link	c.*47C>G		3_prime_UTR_variant	Exon 12 of 12	ENST00000316694.8	NP_004160.3	P34896-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SHMT1	ENST00000316694.8 link	c.*47C>G		3_prime_UTR_variant	Exon 12 of 12	1	NM_004169.5	ENSP00000318868.3		P34896-1

Frequencies

GnomAD3 genomes

AF:

0.262

AC:

39892

AN:

152024

Hom.:

5596

Cov.:

show subpopulations

Gnomad AFR

AF:

0.206

Gnomad AMI

AF:

0.320

Gnomad AMR

AF:

0.227

Gnomad ASJ

AF:

0.314

Gnomad EAS

AF:

0.0739

Gnomad SAS

AF:

0.182

Gnomad FIN

AF:

0.323

Gnomad MID

AF:

0.234

Gnomad NFE

AF:

0.312

Gnomad OTH

AF:

0.259

GnomAD2 exomes

AF:

0.254

AC:

38669

AN:

152280

AF XY:

0.252

show subpopulations

Gnomad AFR exome

AF:

0.197

Gnomad AMR exome

AF:

0.224

Gnomad ASJ exome

AF:

0.322

Gnomad EAS exome

AF:

0.0728

Gnomad FIN exome

AF:

0.338

Gnomad NFE exome

AF:

0.306

Gnomad OTH exome

AF:

0.266

GnomAD4 exome

AF:

0.294

AC:

410382

AN:

1393600

Hom.:

62780

Cov.:

AF XY:

0.291

AC XY:

199887

AN XY:

687528

show subpopulations

African (AFR)

AF:

0.204

AC:

6423

AN:

31534

American (AMR)

AF:

0.222

AC:

7923

AN:

35740

Ashkenazi Jewish (ASJ)

AF:

0.312

AC:

7865

AN:

25172

East Asian (EAS)

AF:

0.0802

AC:

2865

AN:

35744

South Asian (SAS)

AF:

0.179

AC:

14225

AN:

79298

European-Finnish (FIN)

AF:

0.337

AC:

15720

AN:

46592

Middle Eastern (MID)

AF:

0.232

AC:

947

AN:

4074

European-Non Finnish (NFE)

AF:

0.314

AC:

338468

AN:

1077676

Other (OTH)

AF:

0.276

AC:

15946

AN:

57770

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

14548

29096

43643

58191

72739

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11096

22192

33288

44384

55480

<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:

0.262

AC:

39902

AN:

152142

Hom.:

5595

Cov.:

AF XY:

0.259

AC XY:

19233

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.206

AC:

8539

AN:

41522

American (AMR)

AF:

0.227

AC:

3466

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.314

AC:

1089

AN:

3470

East Asian (EAS)

AF:

0.0745

AC:

386

AN:

5182

South Asian (SAS)

AF:

0.183

AC:

881

AN:

4824

European-Finnish (FIN)

AF:

0.323

AC:

3417

AN:

10584

Middle Eastern (MID)

AF:

0.231

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.312

AC:

21225

AN:

67978

Other (OTH)

AF:

0.256

AC:

540

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1522

3043

4565

6086

7608

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

422

844

1266

1688

2110

<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:

0.300

Hom.:

1457

Bravo

AF:

0.248

Asia WGS

AF:

0.137

AC:

477

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

1.3

(source)

DANN

Benign

0.68

PhyloP100

-1.2

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