17-18333025-G-A

Variant summary

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

The NM_004169.5(SHMT1):​c.1054+141C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 1,087,362 control chromosomes in the GnomAD database, including 30,478 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 0.22 ( 3856 hom., cov: 33)
Exomes 𝑓: 0.24 ( 26622 hom. )

Consequence

SHMT1
NM_004169.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.678
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 -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.94).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.285 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SHMT1NM_004169.5 linkuse as main transcriptc.1054+141C>T intron_variant ENST00000316694.8 NP_004160.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SHMT1ENST00000316694.8 linkuse as main transcriptc.1054+141C>T intron_variant 1 NM_004169.5 ENSP00000318868 P1P34896-1

Frequencies

GnomAD3 genomes
AF:
0.219
AC:
33336
AN:
152122
Hom.:
3850
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.152
Gnomad AMI
AF:
0.164
Gnomad AMR
AF:
0.238
Gnomad ASJ
AF:
0.260
Gnomad EAS
AF:
0.297
Gnomad SAS
AF:
0.179
Gnomad FIN
AF:
0.275
Gnomad MID
AF:
0.209
Gnomad NFE
AF:
0.242
Gnomad OTH
AF:
0.225
GnomAD3 exomes
AF:
0.238
AC:
42390
AN:
178122
Hom.:
5142
AF XY:
0.237
AC XY:
22860
AN XY:
96580
show subpopulations
Gnomad AFR exome
AF:
0.146
Gnomad AMR exome
AF:
0.245
Gnomad ASJ exome
AF:
0.261
Gnomad EAS exome
AF:
0.308
Gnomad SAS exome
AF:
0.189
Gnomad FIN exome
AF:
0.267
Gnomad NFE exome
AF:
0.245
Gnomad OTH exome
AF:
0.247
GnomAD4 exome
AF:
0.236
AC:
220722
AN:
935122
Hom.:
26622
Cov.:
12
AF XY:
0.235
AC XY:
113128
AN XY:
482062
show subpopulations
Gnomad4 AFR exome
AF:
0.152
Gnomad4 AMR exome
AF:
0.248
Gnomad4 ASJ exome
AF:
0.268
Gnomad4 EAS exome
AF:
0.247
Gnomad4 SAS exome
AF:
0.193
Gnomad4 FIN exome
AF:
0.262
Gnomad4 NFE exome
AF:
0.239
Gnomad4 OTH exome
AF:
0.238
GnomAD4 genome
AF:
0.219
AC:
33360
AN:
152240
Hom.:
3856
Cov.:
33
AF XY:
0.218
AC XY:
16255
AN XY:
74418
show subpopulations
Gnomad4 AFR
AF:
0.152
Gnomad4 AMR
AF:
0.239
Gnomad4 ASJ
AF:
0.260
Gnomad4 EAS
AF:
0.297
Gnomad4 SAS
AF:
0.180
Gnomad4 FIN
AF:
0.275
Gnomad4 NFE
AF:
0.243
Gnomad4 OTH
AF:
0.223
Alfa
AF:
0.230
Hom.:
773
Bravo
AF:
0.220
Asia WGS
AF:
0.199
AC:
693
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.94
CADD
Benign
7.5
DANN
Benign
0.66

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: rs2273029; hg19: chr17-18236339; COSMIC: COSV57397540; COSMIC: COSV57397540; API