Variant 9-6644547-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_000170.3(GLDC):c.334+67G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000664 in 1,102,630 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0028 ( 8 hom., cov: 31)

Exomes 𝑓: 0.00031 ( 2 hom. )

Consequence

GLDC
NM_000170.3 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.125

Variant links:

Genes affected

GLDC (HGNC:4313): (glycine decarboxylase) 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 P protein, which binds to glycine and enables the methylamine group from glycine to be transferred to the T protein. Defects in this gene are a cause of nonketotic hyperglycinemia (NKH).[provided by RefSeq, Jan 2010]

GLDC links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 9-6644547-C-G is Benign according to our data. Variant chr9-6644547-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 1211882.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GLDC	NM_000170.3 linkuse as main transcript	c.334+67G>C		intron_variant		ENST00000321612.8	NP_000161.2

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris
GLDC	ENST00000321612.8 linkuse as main transcript	c.334+67G>C	intron_variant		1	NM_000170.3	ENSP00000370737	P1
GLDC	ENST00000639364.1 linkuse as main transcript	n.18G>C	non_coding_transcript_exon_variant	1/24	5
GLDC	ENST00000639954.1 linkuse as main transcript	n.178+67G>C	intron_variant, non_coding_transcript_variant		5
GLDC	ENST00000640592.1 linkuse as main transcript	n.217+67G>C	intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.00284

AC:

432

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00987

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00111

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00239

GnomAD4 exome

AF:

0.000315

AC:

299

AN:

950354

Hom.:

Cov.:

AF XY:

0.000237

AC XY:

117

AN XY:

494270

show subpopulations

Gnomad4 AFR exome

AF:

0.00931

Gnomad4 AMR exome

AF:

0.000810

Gnomad4 ASJ exome

AF:

0.0000438

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000397

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000849

GnomAD4 genome

AF:

0.00284

AC:

433

AN:

152276

Hom.:

Cov.:

AF XY:

0.00267

AC XY:

199

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.00987

Gnomad4 AMR

AF:

0.00111

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00236

Alfa

AF:

0.00229

Hom.:

Bravo

AF:

0.00343

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 18, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

5.8

DANN

Benign

0.35

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