Variant rs2273026 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000316694.8(SHMT1):c.242+7G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 1,613,322 control chromosomes in the GnomAD database, including 10,996 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.11 ( 990 hom., cov: 32)

Exomes 𝑓: 0.11 ( 10006 hom. )

Consequence

SHMT1
ENST00000316694.8 splice_region, intron

Scores

Splicing: ADA: 0.00003110

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.96

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.172 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SHMT1	NM_004169.5 linkuse as main transcript	c.242+7G>A		splice_region_variant, intron_variant		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.242+7G>A		splice_region_variant, intron_variant		1	NM_004169.5	ENSP00000318868	P1	P34896-1

Frequencies

GnomAD3 genomes

AF:

0.108

AC:

16408

AN:

151988

Hom.:

992

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0882

Gnomad AMI

AF:

0.0725

Gnomad AMR

AF:

0.160

Gnomad ASJ

AF:

0.0776

Gnomad EAS

AF:

0.161

Gnomad SAS

AF:

0.183

Gnomad FIN

AF:

0.0952

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.103

Gnomad OTH

AF:

0.114

GnomAD3 exomes

AF:

0.122

AC:

30730

AN:

251438

Hom.:

2134

AF XY:

0.123

AC XY:

16650

AN XY:

135902

show subpopulations

Gnomad AFR exome

AF:

0.0901

Gnomad AMR exome

AF:

0.193

Gnomad ASJ exome

AF:

0.0811

Gnomad EAS exome

AF:

0.140

Gnomad SAS exome

AF:

0.178

Gnomad FIN exome

AF:

0.0952

Gnomad NFE exome

AF:

0.0973

Gnomad OTH exome

AF:

0.101

GnomAD4 exome

AF:

0.112

AC:

163481

AN:

1461216

Hom.:

10006

Cov.:

AF XY:

0.114

AC XY:

82916

AN XY:

726962

show subpopulations

Gnomad4 AFR exome

AF:

0.0894

Gnomad4 AMR exome

AF:

0.187

Gnomad4 ASJ exome

AF:

0.0820

Gnomad4 EAS exome

AF:

0.178

Gnomad4 SAS exome

AF:

0.180

Gnomad4 FIN exome

AF:

0.0992

Gnomad4 NFE exome

AF:

0.103

Gnomad4 OTH exome

AF:

0.110

GnomAD4 genome

AF:

0.108

AC:

16405

AN:

152106

Hom.:

990

Cov.:

AF XY:

0.111

AC XY:

8278

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.0880

Gnomad4 AMR

AF:

0.161

Gnomad4 ASJ

AF:

0.0776

Gnomad4 EAS

AF:

0.161

Gnomad4 SAS

AF:

0.182

Gnomad4 FIN

AF:

0.0952

Gnomad4 NFE

AF:

0.103

Gnomad4 OTH

AF:

0.113

Alfa

AF:

0.105

Hom.:

834

Bravo

AF:

0.108

Asia WGS

AF:

0.148

AC:

513

AN:

3478

EpiCase

AF:

0.0960

EpiControl

AF:

0.0927

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

7.7

DANN

Benign

0.54

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000031

dbscSNV1_RF

Benign

0.060

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over