16-81090670-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_004483.5(GCSH):c.159C>T(p.Phe53Phe) variant causes a synonymous change. The variant allele was found at a frequency of 0.0657 in 1,609,126 control chromosomes in the GnomAD database, including 4,042 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.057 ( 257 hom., cov: 32)

Exomes 𝑓: 0.067 ( 3785 hom. )

Consequence

GCSH
NM_004483.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 4.11

Publications

17 publications found

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 Gene-Disease associations (from GenCC):

glycine encephalopathy
Inheritance: AR Classification: STRONG, LIMITED Submitted by: ClinGen, Ambry Genetics
multiple mitochondrial dysfunctions syndrome 7
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, 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

GCSH links:

ENSG00000284512 (HGNC:):

ENSG00000284512 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.39).

BP6

Variant 16-81090670-G-A is Benign according to our data. Variant chr16-81090670-G-A is described in ClinVar as Benign. ClinVar VariationId is 1166773.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0717 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004483.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GCSH	NM_004483.5	MANE Select	c.159C>T	p.Phe53Phe	synonymous	Exon 2 of 5	NP_004474.2
	GCSH	NR_033249.2		n.276C>T		non_coding_transcript_exon	Exon 2 of 4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
GCSH	ENST00000315467.9	TSL:1 MANE Select	c.159C>T	p.Phe53Phe	synonymous	Exon 2 of 5	ENSP00000319531.3
ENSG00000284512	ENST00000640345.1	TSL:5	c.159C>T	p.Phe53Phe	synonymous	Exon 2 of 6	ENSP00000492798.1
ENSG00000260643	ENST00000564536.2	TSL:5	c.159C>T	p.Phe53Phe	synonymous	Exon 2 of 6	ENSP00000491651.1

Frequencies

GnomAD3 genomes

AF:

0.0571

AC:

8686

AN:

152074

Hom.:

255

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0352

Gnomad AMI

AF:

0.00768

Gnomad AMR

AF:

0.0482

Gnomad ASJ

AF:

0.0291

Gnomad EAS

AF:

0.00115

Gnomad SAS

AF:

0.0247

Gnomad FIN

AF:

0.108

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.0734

Gnomad OTH

AF:

0.0506

GnomAD2 exomes

AF:

0.0540

AC:

13570

AN:

251404

AF XY:

0.0541

show subpopulations

Gnomad AFR exome

AF:

0.0391

Gnomad AMR exome

AF:

0.0265

Gnomad ASJ exome

AF:

0.0300

Gnomad EAS exome

AF:

0.00114

Gnomad FIN exome

AF:

0.107

Gnomad NFE exome

AF:

0.0728

Gnomad OTH exome

AF:

0.0554

GnomAD4 exome

AF:

0.0666

AC:

96966

AN:

1456934

Hom.:

3785

Cov.:

AF XY:

0.0652

AC XY:

47297

AN XY:

725144

show subpopulations

African (AFR)

AF:

0.0336

AC:

1124

AN:

33414

American (AMR)

AF:

0.0286

AC:

1279

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0295

AC:

770

AN:

26110

East Asian (EAS)

AF:

0.000504

AC:

AN:

39682

South Asian (SAS)

AF:

0.0256

AC:

2208

AN:

86192

European-Finnish (FIN)

AF:

0.105

AC:

5619

AN:

53408

Middle Eastern (MID)

AF:

0.0391

AC:

225

AN:

5756

European-Non Finnish (NFE)

AF:

0.0742

AC:

82121

AN:

1107402

Other (OTH)

AF:

0.0598

AC:

3600

AN:

60246

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.447

Heterozygous variant carriers

4220

8440

12660

16880

21100

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2926

5852

8778

11704

14630

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0572

AC:

8698

AN:

152192

Hom.:

257

Cov.:

AF XY:

0.0575

AC XY:

4279

AN XY:

74396

show subpopulations

African (AFR)

AF:

0.0354

AC:

1470

AN:

41544

American (AMR)

AF:

0.0482

AC:

735

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.0291

AC:

101

AN:

3470

East Asian (EAS)

AF:

0.00116

AC:

AN:

5184

South Asian (SAS)

AF:

0.0241

AC:

116

AN:

4820

European-Finnish (FIN)

AF:

0.108

AC:

1147

AN:

10584

Middle Eastern (MID)

AF:

0.0510

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0734

AC:

4991

AN:

68010

Other (OTH)

AF:

0.0520

AC:

110

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

427

854

1282

1709

2136

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

196

294

392

490

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0656

Hom.:

491

Bravo

AF:

0.0514

Asia WGS

AF:

0.0170

AC:

AN:

3478

EpiCase

AF:

0.0682

EpiControl

AF:

0.0666

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

May 04, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Glycine encephalopathy

Benign:1

Jan 27, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.39

CADD

Benign

(source)

DANN

Benign

0.86

PhyloP100

4.1

PromoterAI

0.00020

Neutral

(source)

Mutation Taster

=97/3

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over