Variant 16-81084602-GA-GAA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_004483.5(GCSH):c.293-9_293-8insT variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00288 in 1,593,298 control chromosomes in the GnomAD database, including 85 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.015 ( 45 hom., cov: 33)

Exomes 𝑓: 0.0016 ( 40 hom. )

Consequence

GCSH
NM_004483.5 splice_polypyrimidine_tract, intron

Scores

Not classified

Clinical Significance

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

Conservation

PhyloP100: 1.13

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 -16 ACMG points.

BP6

Variant 16-81084602-G-GA is Benign according to our data. Variant chr16-81084602-G-GA is described in ClinVar as [Benign]. Clinvar id is 235601.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0148 (2220/150192) while in subpopulation AFR AF= 0.0505 (2069/40966). AF 95% confidence interval is 0.0487. There are 45 homozygotes in gnomad4. There are 1037 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 45 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GCSH	NM_004483.5 linkuse as main transcript	c.293-9_293-8insT		splice_polypyrimidine_tract_variant, intron_variant		ENST00000315467.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GCSH	ENST00000315467.9 linkuse as main transcript	c.293-9_293-8insT		splice_polypyrimidine_tract_variant, intron_variant		1	NM_004483.5	P1

Frequencies

GnomAD3 genomes

AF:

0.0148

AC:

2218

AN:

150098

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0506

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00530

Gnomad ASJ

AF:

0.00751

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00321

Gnomad NFE

AF:

0.000399

Gnomad OTH

AF:

0.00824

GnomAD3 exomes

AF:

0.00401

AC:

930

AN:

231840

Hom.:

AF XY:

0.00325

AC XY:

410

AN XY:

126148

show subpopulations

Gnomad AFR exome

AF:

0.0504

Gnomad AMR exome

AF:

0.00304

Gnomad ASJ exome

AF:

0.00784

Gnomad EAS exome

AF:

0.0000582

Gnomad SAS exome

AF:

0.0000349

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000339

Gnomad OTH exome

AF:

0.00191

GnomAD4 exome

AF:

0.00164

AC:

2373

AN:

1443106

Hom.:

Cov.:

AF XY:

0.00150

AC XY:

1074

AN XY:

718358

show subpopulations

Gnomad4 AFR exome

AF:

0.0469

Gnomad4 AMR exome

AF:

0.00344

Gnomad4 ASJ exome

AF:

0.00754

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000589

Gnomad4 FIN exome

AF:

0.0000564

Gnomad4 NFE exome

AF:

0.000200

Gnomad4 OTH exome

AF:

0.00413

GnomAD4 genome

AF:

0.0148

AC:

2220

AN:

150192

Hom.:

Cov.:

AF XY:

0.0142

AC XY:

1037

AN XY:

73126

show subpopulations

Gnomad4 AFR

AF:

0.0505

Gnomad4 AMR

AF:

0.00529

Gnomad4 ASJ

AF:

0.00751

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000399

Gnomad4 OTH

AF:

0.00816

Bravo

AF:

0.0176

Asia WGS

AF:

0.00260

AC:

AN:

3478

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

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Jun 04, 2015

- -

Non-ketotic hyperglycinemia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Nov 06, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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