Variant rs8177907 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_004483.5(GCSH):c.252T>C(p.Tyr84=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00826 in 1,611,414 control chromosomes in the GnomAD database, including 573 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.037 ( 287 hom., cov: 32)

Exomes 𝑓: 0.0053 ( 286 hom. )

Consequence

GCSH
NM_004483.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.818

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.37).

BP6

Variant 16-81087641-A-G is Benign according to our data. Variant chr16-81087641-A-G is described in ClinVar as [Benign]. Clinvar id is 462902.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.818 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	UniProt
GCSH	NM_004483.5 linkuse as main transcript	c.252T>C	p.Tyr84=	synonymous_variant	3/5	ENST00000315467.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GCSH	ENST00000315467.9 linkuse as main transcript	c.252T>C	p.Tyr84=	synonymous_variant	3/5	1	NM_004483.5	P1

Frequencies

GnomAD3 genomes

AF:

0.0370

AC:

5628

AN:

152158

Hom.:

286

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:

0.00146

Gnomad OTH

AF:

0.0291

GnomAD3 exomes

AF:

0.0122

AC:

3059

AN:

251206

Hom.:

123

AF XY:

0.00989

AC XY:

1343

AN XY:

135830

show subpopulations

Gnomad AFR exome

AF:

0.122

Gnomad AMR exome

AF:

0.00697

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:

0.00526

AC:

7668

AN:

1459138

Hom.:

286

Cov.:

AF XY:

0.00493

AC XY:

3579

AN XY:

726110

show subpopulations

Gnomad4 AFR exome

AF:

0.118

Gnomad4 AMR exome

AF:

0.00821

Gnomad4 ASJ exome

AF:

0.0317

Gnomad4 EAS exome

AF:

0.0156

Gnomad4 SAS exome

AF:

0.00239

Gnomad4 FIN exome

AF:

0.000113

Gnomad4 NFE exome

AF:

0.000834

Gnomad4 OTH exome

AF:

0.0122

GnomAD4 genome

AF:

0.0371

AC:

5646

AN:

152276

Hom.:

287

Cov.:

AF XY:

0.0359

AC XY:

2674

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.122

Gnomad4 AMR

AF:

0.0131

Gnomad4 ASJ

AF:

0.0346

Gnomad4 EAS

AF:

0.0139

Gnomad4 SAS

AF:

0.00435

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00146

Gnomad4 OTH

AF:

0.0288

Alfa

AF:

0.0119

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:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 04, 2021

- -

Non-ketotic hyperglycinemia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 06, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.37

CADD

Benign

4.5

DANN

Benign

0.84

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