16-81082702-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.24

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]

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 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	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	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.: 16

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

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.: 0 AF XY: 0.0663 AC XY: 15152 AN XY: 228684

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.: 16 AF XY: 0.0553 AC XY: 3261 AN XY: 58992

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.: 48

Bravo AF: 0.0583

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 20, 2021

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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

Other links and lift over

dbSNP: rs200021264; hg19: chr16-81116307;