chr16-81082702-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004483.5(GCSH):​c.*164C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.057 ( 232 hom., cov: 16)
Exomes 𝑓: 0.067 ( 1092 hom. )

Consequence

GCSH
NM_004483.5 3_prime_UTR

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.24
Variant links:
Genes affected
GCSH (HGNC:4208): (glycine cleavage system protein H) 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 H protein, which transfers the methylamine group of glycine from the P protein to the T protein. Defects in this gene are a cause of nonketotic hyperglycinemia (NKH). Two transcript variants, one protein-coding and the other probably not protein-coding,have been found for this gene. Also, several transcribed and non-transcribed pseudogenes of this gene exist throughout the genome.[provided by RefSeq, Jan 2010]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.87).
BP6
Variant 16-81082702-G-C is Benign according to our data. Variant chr16-81082702-G-C is described in ClinVar as [Benign]. Clinvar id is 1177967.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0655 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GCSHNM_004483.5 linkuse as main transcriptc.*164C>G 3_prime_UTR_variant 5/5 ENST00000315467.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GCSHENST00000315467.9 linkuse as main transcriptc.*164C>G 3_prime_UTR_variant 5/51 NM_004483.5 P1

Frequencies

GnomAD3 genomes
AF:
0.0574
AC:
7222
AN:
125818
Hom.:
232
Cov.:
16
show subpopulations
Gnomad AFR
AF:
0.0410
Gnomad AMI
AF:
0.0622
Gnomad AMR
AF:
0.0445
Gnomad ASJ
AF:
0.134
Gnomad EAS
AF:
0.0424
Gnomad SAS
AF:
0.0406
Gnomad FIN
AF:
0.0456
Gnomad MID
AF:
0.134
Gnomad NFE
AF:
0.0672
Gnomad OTH
AF:
0.0697
GnomAD3 exomes
AF:
0.0609
AC:
4762
AN:
78238
Hom.:
144
AF XY:
0.0616
AC XY:
2528
AN XY:
41012
show subpopulations
Gnomad AFR exome
AF:
0.0403
Gnomad AMR exome
AF:
0.0438
Gnomad ASJ exome
AF:
0.142
Gnomad EAS exome
AF:
0.0449
Gnomad SAS exome
AF:
0.0502
Gnomad FIN exome
AF:
0.0567
Gnomad NFE exome
AF:
0.0702
Gnomad OTH exome
AF:
0.0750
GnomAD4 exome
AF:
0.0665
AC:
28490
AN:
428366
Hom.:
1092
Cov.:
0
AF XY:
0.0663
AC XY:
15152
AN XY:
228684
show subpopulations
Gnomad4 AFR exome
AF:
0.0407
Gnomad4 AMR exome
AF:
0.0433
Gnomad4 ASJ exome
AF:
0.136
Gnomad4 EAS exome
AF:
0.0621
Gnomad4 SAS exome
AF:
0.0537
Gnomad4 FIN exome
AF:
0.0524
Gnomad4 NFE exome
AF:
0.0690
Gnomad4 OTH exome
AF:
0.0763
GnomAD4 genome
AF:
0.0573
AC:
7220
AN:
125912
Hom.:
232
Cov.:
16
AF XY:
0.0553
AC XY:
3261
AN XY:
58992
show subpopulations
Gnomad4 AFR
AF:
0.0409
Gnomad4 AMR
AF:
0.0444
Gnomad4 ASJ
AF:
0.134
Gnomad4 EAS
AF:
0.0425
Gnomad4 SAS
AF:
0.0405
Gnomad4 FIN
AF:
0.0456
Gnomad4 NFE
AF:
0.0672
Gnomad4 OTH
AF:
0.0682
Alfa
AF:
0.0698
Hom.:
48
Bravo
AF:
0.0583

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingGeneDxMay 20, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.87
CADD
Benign
0.89
DANN
Benign
0.52

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: rs200021264; hg19: chr16-81116307; API