Variant 16-81082702-G-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.*164C>G 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 0.057 ( 232 hom., cov: 16)

Exomes 𝑓: 0.067 ( 1092 hom. )

Consequence

GCSH
NM_004483.5 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.24

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=-0.87).

BP6

Variant 16-81082702-G-C is Benign according to our data. Variant chr16-81082702-G-C is described in ClinVar as [Benign]. Clinvar id is 1177967.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0655 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.*164C>G		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.*164C>G		3_prime_UTR_variant	5/5	1	NM_004483.5	P1

Frequencies

GnomAD3 genomes

AF:

0.0574

AC:

7222

AN:

125818

Hom.:

232

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0410

Gnomad AMI

AF:

0.0622

Gnomad AMR

AF:

0.0445

Gnomad ASJ

AF:

0.134

Gnomad EAS

AF:

0.0424

Gnomad SAS

AF:

0.0406

Gnomad FIN

AF:

0.0456

Gnomad MID

AF:

0.134

Gnomad NFE

AF:

0.0672

Gnomad OTH

AF:

0.0697

GnomAD3 exomes

AF:

0.0609

AC:

4762

AN:

78238

Hom.:

144

AF XY:

0.0616

AC XY:

2528

AN XY:

41012

show subpopulations

Gnomad AFR exome

AF:

0.0403

Gnomad AMR exome

AF:

0.0438

Gnomad ASJ exome

AF:

0.142

Gnomad EAS exome

AF:

0.0449

Gnomad SAS exome

AF:

0.0502

Gnomad FIN exome

AF:

0.0567

Gnomad NFE exome

AF:

0.0702

Gnomad OTH exome

AF:

0.0750

GnomAD4 exome

AF:

0.0665

AC:

28490

AN:

428366

Hom.:

1092

Cov.:

AF XY:

0.0663

AC XY:

15152

AN XY:

228684

show subpopulations

Gnomad4 AFR exome

AF:

0.0407

Gnomad4 AMR exome

AF:

0.0433

Gnomad4 ASJ exome

AF:

0.136

Gnomad4 EAS exome

AF:

0.0621

Gnomad4 SAS exome

AF:

0.0537

Gnomad4 FIN exome

AF:

0.0524

Gnomad4 NFE exome

AF:

0.0690

Gnomad4 OTH exome

AF:

0.0763

GnomAD4 genome

AF:

0.0573

AC:

7220

AN:

125912

Hom.:

232

Cov.:

AF XY:

0.0553

AC XY:

3261

AN XY:

58992

show subpopulations

Gnomad4 AFR

AF:

0.0409

Gnomad4 AMR

AF:

0.0444

Gnomad4 ASJ

AF:

0.134

Gnomad4 EAS

AF:

0.0425

Gnomad4 SAS

AF:

0.0405

Gnomad4 FIN

AF:

0.0456

Gnomad4 NFE

AF:

0.0672

Gnomad4 OTH

AF:

0.0682

Alfa

AF:

0.0698

Hom.:

Bravo

AF:

0.0583

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 20, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.89

DANN

Benign

0.52

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