Variant chr16-81082778-T-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_004483.5(GCSH):c.*88A>C 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 0.10 ( 798 hom., cov: 19)

Exomes 𝑓: 0.096 ( 3168 hom. )

Consequence

GCSH
NM_004483.5 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.21

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:

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=-0.88).

BP6

Variant 16-81082778-T-G is Benign according to our data. Variant chr16-81082778-T-G is described in ClinVar as [Benign]. Clinvar id is 1290759.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.19 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.*88A>C		3_prime_UTR_variant	5/5	ENST00000315467.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GCSH	ENST00000315467.9 linkuse as main transcript	c.*88A>C		3_prime_UTR_variant	5/5	1	NM_004483.5	P1

Frequencies

GnomAD3 genomes

AF:

0.104

AC:

14194

AN:

136424

Hom.:

796

Cov.:

show subpopulations

Gnomad AFR

AF:

0.148

Gnomad AMI

AF:

0.00799

Gnomad AMR

AF:

0.109

Gnomad ASJ

AF:

0.0764

Gnomad EAS

AF:

0.202

Gnomad SAS

AF:

0.0977

Gnomad FIN

AF:

0.105

Gnomad MID

AF:

0.0812

Gnomad NFE

AF:

0.0746

Gnomad OTH

AF:

0.0910

GnomAD3 exomes

AF:

0.111

AC:

21102

AN:

189860

Hom.:

1385

AF XY:

0.106

AC XY:

10859

AN XY:

102806

show subpopulations

Gnomad AFR exome

AF:

0.164

Gnomad AMR exome

AF:

0.158

Gnomad ASJ exome

AF:

0.0763

Gnomad EAS exome

AF:

0.214

Gnomad SAS exome

AF:

0.0927

Gnomad FIN exome

AF:

0.121

Gnomad NFE exome

AF:

0.0771

Gnomad OTH exome

AF:

0.0962

GnomAD4 exome

AF:

0.0963

AC:

55075

AN:

572180

Hom.:

3168

Cov.:

AF XY:

0.0939

AC XY:

28869

AN XY:

307390

show subpopulations

Gnomad4 AFR exome

AF:

0.159

Gnomad4 AMR exome

AF:

0.152

Gnomad4 ASJ exome

AF:

0.0741

Gnomad4 EAS exome

AF:

0.210

Gnomad4 SAS exome

AF:

0.0893

Gnomad4 FIN exome

AF:

0.119

Gnomad4 NFE exome

AF:

0.0750

Gnomad4 OTH exome

AF:

0.0967

GnomAD4 genome

AF:

0.104

AC:

14219

AN:

136544

Hom.:

798

Cov.:

AF XY:

0.105

AC XY:

6890

AN XY:

65366

show subpopulations

Gnomad4 AFR

AF:

0.149

Gnomad4 AMR

AF:

0.109

Gnomad4 ASJ

AF:

0.0764

Gnomad4 EAS

AF:

0.201

Gnomad4 SAS

AF:

0.0957

Gnomad4 FIN

AF:

0.105

Gnomad4 NFE

AF:

0.0747

Gnomad4 OTH

AF:

0.0933

Alfa

AF:

0.0913

Hom.:

113

Bravo

AF:

0.116

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 submitter	clinical testing	GeneDx	May 12, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

DANN

Benign

0.62

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