rs74461075

Positions:

Variant summary

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

The ENST00000321612.8(GLDC):​c.1815C>T​(p.Leu605=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00236 in 1,613,850 control chromosomes in the GnomAD database, including 60 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.012 ( 26 hom., cov: 32)
Exomes 𝑓: 0.0013 ( 34 hom. )

Consequence

GLDC
ENST00000321612.8 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 1.28
Variant links:
Genes affected
GLDC (HGNC:4313): (glycine decarboxylase) Degradation of glycine is brought about by the glycine cleavage system, which is composed of four mitochondrial protein components: P protein (a pyridoxal phosphate-dependent glycine decarboxylase), H protein (a lipoic acid-containing protein), T protein (a tetrahydrofolate-requiring enzyme), and L protein (a lipoamide dehydrogenase). The protein encoded by this gene is the P protein, which binds to glycine and enables the methylamine group from glycine to be transferred to the T protein. Defects in this gene are a cause of nonketotic hyperglycinemia (NKH).[provided by RefSeq, Jan 2010]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.4).
BP6
Variant 9-6587176-G-A is Benign according to our data. Variant chr9-6587176-G-A is described in ClinVar as [Benign]. Clinvar id is 367185.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=1.28 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0123 (1879/152302) while in subpopulation AFR AF= 0.0428 (1777/41550). AF 95% confidence interval is 0.0411. There are 26 homozygotes in gnomad4. There are 906 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 26 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
GLDCNM_000170.3 linkuse as main transcriptc.1815C>T p.Leu605= synonymous_variant 15/25 ENST00000321612.8 NP_000161.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
GLDCENST00000321612.8 linkuse as main transcriptc.1815C>T p.Leu605= synonymous_variant 15/251 NM_000170.3 ENSP00000370737 P1

Frequencies

GnomAD3 genomes
AF:
0.0123
AC:
1869
AN:
152184
Hom.:
26
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0426
Gnomad AMI
AF:
0.00110
Gnomad AMR
AF:
0.00432
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000147
Gnomad OTH
AF:
0.0115
GnomAD3 exomes
AF:
0.00318
AC:
799
AN:
251474
Hom.:
15
AF XY:
0.00247
AC XY:
336
AN XY:
135912
show subpopulations
Gnomad AFR exome
AF:
0.0424
Gnomad AMR exome
AF:
0.00234
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000653
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000141
Gnomad OTH exome
AF:
0.00163
GnomAD4 exome
AF:
0.00132
AC:
1927
AN:
1461548
Hom.:
34
Cov.:
31
AF XY:
0.00112
AC XY:
811
AN XY:
727120
show subpopulations
Gnomad4 AFR exome
AF:
0.0426
Gnomad4 AMR exome
AF:
0.00259
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000928
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000139
Gnomad4 OTH exome
AF:
0.00343
GnomAD4 genome
AF:
0.0123
AC:
1879
AN:
152302
Hom.:
26
Cov.:
32
AF XY:
0.0122
AC XY:
906
AN XY:
74484
show subpopulations
Gnomad4 AFR
AF:
0.0428
Gnomad4 AMR
AF:
0.00431
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000147
Gnomad4 OTH
AF:
0.0114
Alfa
AF:
0.00289
Hom.:
4
Bravo
AF:
0.0139
Asia WGS
AF:
0.00635
AC:
22
AN:
3478
EpiCase
AF:
0.000327
EpiControl
AF:
0.000296

ClinVar

Significance: Benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Non-ketotic hyperglycinemia Benign:3
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 31, 2024- -
Benign, no assertion criteria providedclinical testingNatera, Inc.Sep 16, 2020- -
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 12, 2018This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
not provided Benign:2
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingGeneDxSep 09, 2020- -
not specified Benign:1
Benign, criteria provided, single submitterclinical testingAthena DiagnosticsNov 08, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.40
CADD
Benign
6.6
DANN
Benign
0.77

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: rs74461075; hg19: chr9-6587176; API