Variant rs8177876 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_004483.5(GCSH):c.159C>T(p.Phe53Phe) variant causes a synonymous change. The variant allele was found at a frequency of 0.0657 in 1,609,126 control chromosomes in the GnomAD database, including 4,042 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.057 ( 257 hom., cov: 32)

Exomes 𝑓: 0.067 ( 3785 hom. )

Consequence

GCSH
NM_004483.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 4.11

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]

GCSH links:

ENSG00000284512 (HGNC:):

ENSG00000284512 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.39).

BP6

Variant 16-81090670-G-A is Benign according to our data. Variant chr16-81090670-G-A is described in ClinVar as [Benign]. Clinvar id is 1166773.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-81090670-G-A is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0717 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GCSH	NM_004483.5 linkuse as main transcript	c.159C>T	p.Phe53Phe	synonymous_variant	2/5	ENST00000315467.9	NP_004474.2	P23434

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
GCSH	ENST00000315467.9 linkuse as main transcript	c.159C>T	p.Phe53Phe	synonymous_variant	2/5	1	NM_004483.5	ENSP00000319531.3	P23434
ENSG00000284512	ENST00000640345.1 linkuse as main transcript	c.159C>T	p.Phe53Phe	synonymous_variant	2/6	5		ENSP00000492798.1	A0A1W2PS29
ENSG00000260643	ENST00000564536.2 linkuse as main transcript	c.159C>T	p.Phe53Phe	synonymous_variant	2/6	5		ENSP00000491651.1	A0A1W2PPQ1

Frequencies

GnomAD3 genomes

AF:

0.0571

AC:

8686

AN:

152074

Hom.:

255

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0352

Gnomad AMI

AF:

0.00768

Gnomad AMR

AF:

0.0482

Gnomad ASJ

AF:

0.0291

Gnomad EAS

AF:

0.00115

Gnomad SAS

AF:

0.0247

Gnomad FIN

AF:

0.108

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.0734

Gnomad OTH

AF:

0.0506

GnomAD3 exomes

AF:

0.0540

AC:

13570

AN:

251404

Hom.:

527

AF XY:

0.0541

AC XY:

7357

AN XY:

135900

show subpopulations

Gnomad AFR exome

AF:

0.0391

Gnomad AMR exome

AF:

0.0265

Gnomad ASJ exome

AF:

0.0300

Gnomad EAS exome

AF:

0.00114

Gnomad SAS exome

AF:

0.0248

Gnomad FIN exome

AF:

0.107

Gnomad NFE exome

AF:

0.0728

Gnomad OTH exome

AF:

0.0554

GnomAD4 exome

AF:

0.0666

AC:

96966

AN:

1456934

Hom.:

3785

Cov.:

AF XY:

0.0652

AC XY:

47297

AN XY:

725144

show subpopulations

Gnomad4 AFR exome

AF:

0.0336

Gnomad4 AMR exome

AF:

0.0286

Gnomad4 ASJ exome

AF:

0.0295

Gnomad4 EAS exome

AF:

0.000504

Gnomad4 SAS exome

AF:

0.0256

Gnomad4 FIN exome

AF:

0.105

Gnomad4 NFE exome

AF:

0.0742

Gnomad4 OTH exome

AF:

0.0598

GnomAD4 genome

AF:

0.0572

AC:

8698

AN:

152192

Hom.:

257

Cov.:

AF XY:

0.0575

AC XY:

4279

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.0354

Gnomad4 AMR

AF:

0.0482

Gnomad4 ASJ

AF:

0.0291

Gnomad4 EAS

AF:

0.00116

Gnomad4 SAS

AF:

0.0241

Gnomad4 FIN

AF:

0.108

Gnomad4 NFE

AF:

0.0734

Gnomad4 OTH

AF:

0.0520

Alfa

AF:

0.0676

Hom.:

413

Bravo

AF:

0.0514

Asia WGS

AF:

0.0170

AC:

AN:

3478

EpiCase

AF:

0.0682

EpiControl

AF:

0.0666

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -

Glycine encephalopathy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Benign

0.86

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over