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17-18340104-C-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2

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 (★). Synonymous variant affecting the same amino acid position (i.e. V251V) has been classified as Benign.

Frequency

Genomes: 𝑓 0.0019 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0018 ( 11 hom. )

Consequence

SHMT1
NM_004169.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 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=-0.38).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 17-18340104-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_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=0.141 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
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
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAdExome at 3 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SHMT1NM_004169.5 linkuse as main transcriptc.753G>C p.Val251= synonymous_variant 7/12 ENST00000316694.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SHMT1ENST00000316694.8 linkuse as main transcriptc.753G>C p.Val251= synonymous_variant 7/121 NM_004169.5 P1P34896-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00191
AC:
290
AN:
152204
Hom.:
0
Cov.:
32
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.:
3
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.:
11
Cov.:
31
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
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00191
AC:
291
AN:
152322
Hom.:
0
Cov.:
32
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.:
1
Bravo
AF:
0.00243
Asia WGS
AF:
0.00173
AC:
6
AN:
3478
EpiCase
AF:
0.00393
EpiControl
AF:
0.00379

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 testingInvitaeJul 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.

Other links and lift over

dbSNP: rs141575508; hg19: chr17-18243418; API