Variant rs8177847 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.90C>G(p.Pro30=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00733 in 1,319,306 control chromosomes in the GnomAD database, including 270 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.032 ( 206 hom., cov: 34)

Exomes 𝑓: 0.0041 ( 64 hom. )

Consequence

GCSH
NM_004483.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.728

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 16-81096189-G-C is Benign according to our data. Variant chr16-81096189-G-C is described in ClinVar as [Benign]. Clinvar id is 462910.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.728 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.101 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
GCSH	NM_004483.5 linkuse as main transcript	c.90C>G	p.Pro30=	synonymous_variant	1/5	ENST00000315467.9
GCSH	XM_017023136.3 linkuse as main transcript	c.90C>G	p.Pro30=	synonymous_variant	1/5
GCSH	NR_033249.2 linkuse as main transcript	n.207C>G		non_coding_transcript_exon_variant	1/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GCSH	ENST00000315467.9 linkuse as main transcript	c.90C>G	p.Pro30=	synonymous_variant	1/5	1	NM_004483.5	P1

Frequencies

GnomAD3 genomes

AF:

0.0317

AC:

4825

AN:

152084

Hom.:

205

Cov.:

show subpopulations

Gnomad AFR

AF:

0.104

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0113

Gnomad ASJ

AF:

0.0346

Gnomad EAS

AF:

0.0141

Gnomad SAS

AF:

0.00434

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0255

Gnomad NFE

AF:

0.00128

Gnomad OTH

AF:

0.0249

GnomAD3 exomes

AF:

0.00286

AC:

AN:

5236

Hom.:

AF XY:

0.00214

AC XY:

AN XY:

3272

show subpopulations

Gnomad AFR exome

AF:

0.0517

Gnomad AMR exome

AF:

0.00225

Gnomad ASJ exome

AF:

0.0113

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000756

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00104

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00414

AC:

4829

AN:

1167114

Hom.:

Cov.:

AF XY:

0.00395

AC XY:

2234

AN XY:

565118

show subpopulations

Gnomad4 AFR exome

AF:

0.101

Gnomad4 AMR exome

AF:

0.00953

Gnomad4 ASJ exome

AF:

0.0318

Gnomad4 EAS exome

AF:

0.0177

Gnomad4 SAS exome

AF:

0.00174

Gnomad4 FIN exome

AF:

0.000112

Gnomad4 NFE exome

AF:

0.000747

Gnomad4 OTH exome

AF:

0.0112

GnomAD4 genome

AF:

0.0318

AC:

4841

AN:

152192

Hom.:

206

Cov.:

AF XY:

0.0309

AC XY:

2300

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.104

Gnomad4 AMR

AF:

0.0113

Gnomad4 ASJ

AF:

0.0346

Gnomad4 EAS

AF:

0.0141

Gnomad4 SAS

AF:

0.00393

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00128

Gnomad4 OTH

AF:

0.0246

Alfa

AF:

0.0315

Hom.:

Bravo

AF:

0.0367

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

-0.81

CADD

Benign

6.2

DANN

Benign

0.67

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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