Variant chr17-18340104-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_004169.5(SHMT1):c.753G>C(p.Val251=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00185 in 1,614,126 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0019 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0018 ( 11 hom. )

Consequence

SHMT1
NM_004169.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.141

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 made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.38).

BP6

Variant 17-18340104-C-G is Benign according to our data. Variant chr17-18340104-C-G is described in ClinVar as [Benign]. Clinvar id is 790881.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.141 with no splicing effect.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00184 (2688/1461804) while in subpopulation MID AF= 0.0205 (118/5768). AF 95% confidence interval is 0.0175. There are 11 homozygotes in gnomad4_exome. There are 1415 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 11 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SHMT1	NM_004169.5 linkuse as main transcript	c.753G>C	p.Val251=	synonymous_variant	7/12	ENST00000316694.8	NP_004160.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SHMT1	ENST00000316694.8 linkuse as main transcript	c.753G>C	p.Val251=	synonymous_variant	7/12	1	NM_004169.5	ENSP00000318868	P1	P34896-1

Frequencies

GnomAD3 genomes

AF:

0.00191

AC:

290

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000410

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00281

Gnomad ASJ

AF:

0.00778

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00310

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.00251

Gnomad OTH

AF:

0.00431

GnomAD3 exomes

AF:

0.00245

AC:

615

AN:

251298

Hom.:

AF XY:

0.00278

AC XY:

377

AN XY:

135846

show subpopulations

Gnomad AFR exome

AF:

0.000369

Gnomad AMR exome

AF:

0.00173

Gnomad ASJ exome

AF:

0.00834

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00408

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00260

Gnomad OTH exome

AF:

0.00733

GnomAD4 exome

AF:

0.00184

AC:

2688

AN:

1461804

Hom.:

Cov.:

AF XY:

0.00195

AC XY:

1415

AN XY:

727208

show subpopulations

Gnomad4 AFR exome

AF:

0.000717

Gnomad4 AMR exome

AF:

0.00170

Gnomad4 ASJ exome

AF:

0.00880

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00388

Gnomad4 FIN exome

AF:

0.0000937

Gnomad4 NFE exome

AF:

0.00154

Gnomad4 OTH exome

AF:

0.00316

GnomAD4 genome

AF:

0.00191

AC:

291

AN:

152322

Hom.:

Cov.:

AF XY:

0.00197

AC XY:

147

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.000433

Gnomad4 AMR

AF:

0.00281

Gnomad4 ASJ

AF:

0.00778

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00352

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.00251

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.00295

Hom.:

Bravo

AF:

0.00243

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.00393

EpiControl

AF:

0.00379

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.38

CADD

Benign

6.8

DANN

Benign

0.71

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over