16-81084301-A-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.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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.41

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=-0.93).
• 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_single_submitter, 1 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	c.424+162T>G		intron_variant		ENST00000315467.9

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16899 AN: 152160 Hom.: 997 Cov.: 33

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.: 6 AF XY: 0.0929 AC XY: 26928 AN XY: 289846

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.: 33 AF XY: 0.113 AC XY: 8413 AN XY: 74462

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:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 12, 2021

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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

Other links and lift over

dbSNP: rs56032321; hg19: chr16-81117906; COSMIC: COSV59602102;