dbSNP rs2273028: SHMT1:c.815-23C>T (chr17-18335698-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_004169.5(SHMT1):c.815-23C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.316 in 1,522,650 control chromosomes in the GnomAD database, including 80,193 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 0.36 ( 10871 hom., cov: 32)

Exomes 𝑓: 0.31 ( 69322 hom. )

Consequence

SHMT1
NM_004169.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.390

Publications

24 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:

Genome browser will be placed here

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=-0.87).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.512 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHMT1	NM_004169.5 link	c.815-23C>T		intron_variant	Intron 7 of 11	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.815-23C>T		intron_variant	Intron 7 of 11	1	NM_004169.5	ENSP00000318868.3		P34896-1

Frequencies

GnomAD3 genomes

AF:

0.361

AC:

54778

AN:

151882

Hom.:

10852

Cov.:

show subpopulations

Gnomad AFR

AF:

0.517

Gnomad AMI

AF:

0.318

Gnomad AMR

AF:

0.281

Gnomad ASJ

AF:

0.358

Gnomad EAS

AF:

0.0769

Gnomad SAS

AF:

0.208

Gnomad FIN

AF:

0.325

Gnomad MID

AF:

0.370

Gnomad NFE

AF:

0.323

Gnomad OTH

AF:

0.348

GnomAD2 exomes

AF:

0.294

AC:

73951

AN:

251470

AF XY:

0.288

show subpopulations

Gnomad AFR exome

AF:

0.518

Gnomad AMR exome

AF:

0.257

Gnomad ASJ exome

AF:

0.362

Gnomad EAS exome

AF:

0.0770

Gnomad FIN exome

AF:

0.337

Gnomad NFE exome

AF:

0.317

Gnomad OTH exome

AF:

0.320

GnomAD4 exome

AF:

0.311

AC:

426193

AN:

1370650

Hom.:

69322

Cov.:

AF XY:

0.307

AC XY:

210720

AN XY:

687012

show subpopulations

African (AFR)

AF:

0.523

AC:

16513

AN:

31594

American (AMR)

AF:

0.258

AC:

11493

AN:

44612

Ashkenazi Jewish (ASJ)

AF:

0.354

AC:

9037

AN:

25538

East Asian (EAS)

AF:

0.0811

AC:

3186

AN:

39286

South Asian (SAS)

AF:

0.203

AC:

17104

AN:

84386

European-Finnish (FIN)

AF:

0.339

AC:

18071

AN:

53348

Middle Eastern (MID)

AF:

0.334

AC:

1864

AN:

5586

European-Non Finnish (NFE)

AF:

0.321

AC:

330794

AN:

1029000

Other (OTH)

AF:

0.316

AC:

18131

AN:

57300

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

13901

27802

41704

55605

69506

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10394

20788

31182

41576

51970

<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:

0.361

AC:

54853

AN:

152000

Hom.:

10871

Cov.:

AF XY:

0.355

AC XY:

26393

AN XY:

74290

show subpopulations

African (AFR)

AF:

0.517

AC:

21427

AN:

41418

American (AMR)

AF:

0.281

AC:

4285

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.358

AC:

1241

AN:

3468

East Asian (EAS)

AF:

0.0775

AC:

401

AN:

5174

South Asian (SAS)

AF:

0.210

AC:

1010

AN:

4814

European-Finnish (FIN)

AF:

0.325

AC:

3430

AN:

10570

Middle Eastern (MID)

AF:

0.361

AC:

106

AN:

294

European-Non Finnish (NFE)

AF:

0.323

AC:

21925

AN:

67974

Other (OTH)

AF:

0.349

AC:

738

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1717

3434

5151

6868

8585

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

518

1036

1554

2072

2590

<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:

0.329

Hom.:

33792

Bravo

AF:

0.361

Asia WGS

AF:

0.187

AC:

654

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.54

(source)

DANN

Benign

0.42

PhyloP100

0.39

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