Menu
GeneBe

17-18328822-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_004169.5(SHMT1):c.1380C>T(p.Ala460=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00285 in 1,612,892 control chromosomes in the GnomAD database, including 113 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.016 ( 67 hom., cov: 32)
Exomes 𝑓: 0.0015 ( 46 hom. )

Consequence

SHMT1
NM_004169.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.980
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.76).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 17-18328822-G-A is Benign according to our data. Variant chr17-18328822-G-A is described in ClinVar as [Benign]. Clinvar id is 769910.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.98 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0521 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SHMT1NM_004169.5 linkuse as main transcriptc.1380C>T p.Ala460= synonymous_variant 12/12 ENST00000316694.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SHMT1ENST00000316694.8 linkuse as main transcriptc.1380C>T p.Ala460= synonymous_variant 12/121 NM_004169.5 P1P34896-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0156
AC:
2374
AN:
152152
Hom.:
67
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0539
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00694
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000118
Gnomad OTH
AF:
0.0115
GnomAD3 exomes
AF:
0.00413
AC:
1024
AN:
247926
Hom.:
26
AF XY:
0.00302
AC XY:
406
AN XY:
134360
show subpopulations
Gnomad AFR exome
AF:
0.0550
Gnomad AMR exome
AF:
0.00340
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000986
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000451
Gnomad OTH exome
AF:
0.00213
GnomAD4 exome
AF:
0.00152
AC:
2214
AN:
1460622
Hom.:
46
Cov.:
33
AF XY:
0.00128
AC XY:
931
AN XY:
726488
show subpopulations
Gnomad4 AFR exome
AF:
0.0540
Gnomad4 AMR exome
AF:
0.00365
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.000128
Gnomad4 FIN exome
AF:
0.0000188
Gnomad4 NFE exome
AF:
0.0000297
Gnomad4 OTH exome
AF:
0.00323
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0156
AC:
2380
AN:
152270
Hom.:
67
Cov.:
32
AF XY:
0.0160
AC XY:
1188
AN XY:
74440
show subpopulations
Gnomad4 AFR
AF:
0.0540
Gnomad4 AMR
AF:
0.00693
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000118
Gnomad4 OTH
AF:
0.0113
Alfa
AF:
0.00724
Hom.:
4
Bravo
AF:
0.0175
Asia WGS
AF:
0.00115
AC:
4
AN:
3478
EpiCase
AF:
0.0000545
EpiControl
AF:
0.000119

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.76
Cadd
Benign
0.34
Dann
Benign
0.70

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.

Other links and lift over

dbSNP: rs116100382; hg19: chr17-18232136; API