Variant rs8177908 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_004483.5(GCSH):c.261C>G(p.Leu87Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00822 in 1,611,310 control chromosomes in the GnomAD database, including 564 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.037 ( 286 hom., cov: 32)

Exomes 𝑓: 0.0052 ( 278 hom. )

Consequence

GCSH
NM_004483.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.285

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

Variant 16-81087632-G-C is Benign according to our data. Variant chr16-81087632-G-C is described in ClinVar as [Benign]. Clinvar id is 462903.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.285 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.119 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.261C>G	p.Leu87Leu	synonymous_variant	3/5	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.261C>G	p.Leu87Leu	synonymous_variant	3/5	1	NM_004483.5	ENSP00000319531.3	P23434
ENSG00000284512	ENST00000640345.1 linkuse as main transcript	c.261C>G	p.Leu87Leu	synonymous_variant	3/6	5		ENSP00000492798.1	A0A1W2PS29
ENSG00000260643	ENST00000564536.2 linkuse as main transcript	c.261C>G	p.Leu87Leu	synonymous_variant	3/6	5		ENSP00000491651.1	A0A1W2PPQ1

Frequencies

GnomAD3 genomes

AF:

0.0370

AC:

5625

AN:

152046

Hom.:

285

Cov.:

show subpopulations

Gnomad AFR

AF:

0.122

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0132

Gnomad ASJ

AF:

0.0346

Gnomad EAS

AF:

0.0137

Gnomad SAS

AF:

0.00476

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.00144

Gnomad OTH

AF:

0.0291

GnomAD3 exomes

AF:

0.0122

AC:

3056

AN:

251220

Hom.:

121

AF XY:

0.00989

AC XY:

1344

AN XY:

135842

show subpopulations

Gnomad AFR exome

AF:

0.122

Gnomad AMR exome

AF:

0.00700

Gnomad ASJ exome

AF:

0.0332

Gnomad EAS exome

AF:

0.00946

Gnomad SAS exome

AF:

0.00245

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.00175

Gnomad OTH exome

AF:

0.00897

GnomAD4 exome

AF:

0.00521

AC:

7598

AN:

1459146

Hom.:

278

Cov.:

AF XY:

0.00488

AC XY:

3545

AN XY:

726108

show subpopulations

Gnomad4 AFR exome

AF:

0.116

Gnomad4 AMR exome

AF:

0.00821

Gnomad4 ASJ exome

AF:

0.0315

Gnomad4 EAS exome

AF:

0.0156

Gnomad4 SAS exome

AF:

0.00238

Gnomad4 FIN exome

AF:

0.000112

Gnomad4 NFE exome

AF:

0.000820

Gnomad4 OTH exome

AF:

0.0123

GnomAD4 genome

AF:

0.0371

AC:

5643

AN:

152164

Hom.:

286

Cov.:

AF XY:

0.0359

AC XY:

2672

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.122

Gnomad4 AMR

AF:

0.0132

Gnomad4 ASJ

AF:

0.0346

Gnomad4 EAS

AF:

0.0139

Gnomad4 SAS

AF:

0.00435

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00144

Gnomad4 OTH

AF:

0.0288

Alfa

AF:

0.0168

Hom.:

Bravo

AF:

0.0433

Asia WGS

AF:

0.0160

AC:

AN:

3478

EpiCase

AF:

0.00316

EpiControl

AF:

0.00279

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

Dec 06, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

3.0

DANN

Benign

0.63

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.

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