rs7848919

Variant names:

• chr9-6532477-G-A
• rs7848919
• ENST00000638233.1:n.2038C>T

Your query was ambiguous. Multiple possible variants found:

• chr9-6532477-G-A
• chr9-6532477-G-C
• chr9-6532477-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000638233.1(GLDC):​n.2038C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.707 in 154,584 control chromosomes in the GnomAD database, including 38,956 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.71 (38283 hom., cov: 29)
  • Exomes 𝑓: 0.63 (673 hom.)
• Consequence: GLDC ENST00000638233.1 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.693
• Publications: 14 publications found

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 Gene-Disease associations (from GenCC):

• glycine encephalopathy

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Myriad Women’s Health, Labcorp Genetics (formerly Invitae), ClinGen
• glycine encephalopathy 1

  Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
• infantile glycine encephalopathy

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• neonatal glycine encephalopathy

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• atypical glycine encephalopathy

  Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 9-6532477-G-A is Benign according to our data. Variant chr9-6532477-G-A is described in ClinVar as Benign. ClinVar VariationId is 367162.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.948 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GLDC	NM_000170.3	c.*540C>T		3_prime_UTR_variant	Exon 25 of 25	ENST00000321612.8	NP_000161.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GLDC	ENST00000321612.8	c.*540C>T		3_prime_UTR_variant	Exon 25 of 25	1	NM_000170.3	ENSP00000370737.4

Frequencies

GnomAD3 genomes AF: 0.708 AC: 107145 AN: 151230 Hom.: 38254 Cov.: 29

Gnomad AFR AF: 0.700

Gnomad AMI AF: 0.451

Gnomad AMR AF: 0.756

Gnomad ASJ AF: 0.673

Gnomad EAS AF: 0.971

Gnomad SAS AF: 0.722

Gnomad FIN AF: 0.765

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.680

Gnomad OTH AF: 0.680

GnomAD4 exome AF: 0.629 AC: 2041 AN: 3246 Hom.: 673 Cov.: 0 AF XY: 0.628 AC XY: 1092 AN XY: 1738

African (AFR) AF: 0.250 AC: 1 AN: 4

American (AMR) AF: 0.716 AC: 388 AN: 542

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 2 AN: 8

East Asian (EAS) AF: 1.00 AC: 32 AN: 32

South Asian (SAS) AF: 0.579 AC: 161 AN: 278

European-Finnish (FIN) AF: 0.725 AC: 309 AN: 426

Middle Eastern (MID) AF: 0.500 AC: 1 AN: 2

European-Non Finnish (NFE) AF: 0.585 AC: 1093 AN: 1868

Other (OTH) AF: 0.628 AC: 54 AN: 86

GnomAD4 genome AF: 0.709 AC: 107227 AN: 151338 Hom.: 38283 Cov.: 29 AF XY: 0.715 AC XY: 52828 AN XY: 73900

African (AFR) AF: 0.700 AC: 28790 AN: 41152

American (AMR) AF: 0.756 AC: 11522 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.673 AC: 2334 AN: 3466

East Asian (EAS) AF: 0.971 AC: 5007 AN: 5158

South Asian (SAS) AF: 0.722 AC: 3453 AN: 4784

European-Finnish (FIN) AF: 0.765 AC: 7954 AN: 10396

Middle Eastern (MID) AF: 0.714 AC: 210 AN: 294

European-Non Finnish (NFE) AF: 0.680 AC: 46127 AN: 67856

Other (OTH) AF: 0.680 AC: 1420 AN: 2088

Alfa AF: 0.688 Hom.: 122638

Bravo AF: 0.706

Asia WGS AF: 0.826 AC: 2873 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Glycine encephalopathy Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.2
DANN	Benign	0.62
PhyloP100		0.69
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7848919; hg19: chr9-6532477;