Variant chr16-81084301-A-C 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.424+162T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0984 in 694,126 control chromosomes in the GnomAD database, including 3,892 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 999 hom., cov: 33)

Exomes 𝑓: 0.095 ( 2893 hom. )

Consequence

GCSH
NM_004483.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.41

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=-0.93).

BP6

Variant 16-81084301-A-C is Benign according to our data. Variant chr16-81084301-A-C is described in ClinVar as [Benign]. Clinvar id is 1234127.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.198 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.424+162T>G		intron_variant		ENST00000315467.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GCSH	ENST00000315467.9 linkuse as main transcript	c.424+162T>G		intron_variant		1	NM_004483.5	P1

Frequencies

GnomAD3 genomes

AF:

0.111

AC:

16899

AN:

152160

Hom.:

997

Cov.:

show subpopulations

Gnomad AFR

AF:

0.157

Gnomad AMI

AF:

0.00768

Gnomad AMR

AF:

0.116

Gnomad ASJ

AF:

0.0778

Gnomad EAS

AF:

0.209

Gnomad SAS

AF:

0.104

Gnomad FIN

AF:

0.121

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.0773

Gnomad OTH

AF:

0.0965

GnomAD4 exome

AF:

0.0948

AC:

51357

AN:

541848

Hom.:

2893

Cov.:

AF XY:

0.0929

AC XY:

26928

AN XY:

289846

show subpopulations

Gnomad4 AFR exome

AF:

0.158

Gnomad4 AMR exome

AF:

0.144

Gnomad4 ASJ exome

AF:

0.0753

Gnomad4 EAS exome

AF:

0.208

Gnomad4 SAS exome

AF:

0.0890

Gnomad4 FIN exome

AF:

0.120

Gnomad4 NFE exome

AF:

0.0754

Gnomad4 OTH exome

AF:

0.0972

GnomAD4 genome

AF:

0.111

AC:

16923

AN:

152278

Hom.:

999

Cov.:

AF XY:

0.113

AC XY:

8413

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.157

Gnomad4 AMR

AF:

0.116

Gnomad4 ASJ

AF:

0.0778

Gnomad4 EAS

AF:

0.208

Gnomad4 SAS

AF:

0.102

Gnomad4 FIN

AF:

0.121

Gnomad4 NFE

AF:

0.0773

Gnomad4 OTH

AF:

0.0983

Alfa

AF:

0.0977

Hom.:

100

Bravo

AF:

0.116

Asia WGS

AF:

0.151

AC:

525

AN:

3478

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

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.43

DANN

Benign

0.16

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