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16-81082778-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_004483.5(GCSH):c.*88A>C 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 0.10 ( 798 hom., cov: 19)
Exomes 𝑓: 0.096 ( 3168 hom. )

Consequence

GCSH
NM_004483.5 3_prime_UTR

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.21
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BP6
Variant 16-81082778-T-G is Benign according to our data. Variant chr16-81082778-T-G is described in ClinVar as [Benign]. Clinvar id is 1290759.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GCSHNM_004483.5 linkuse as main transcriptc.*88A>C 3_prime_UTR_variant 5/5 ENST00000315467.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GCSHENST00000315467.9 linkuse as main transcriptc.*88A>C 3_prime_UTR_variant 5/51 NM_004483.5 P1

Frequencies

GnomAD3 genomes
AF:
0.104
AC:
14194
AN:
136424
Hom.:
796
Cov.:
19
show subpopulations
Gnomad AFR
AF:
0.148
Gnomad AMI
AF:
0.00799
Gnomad AMR
AF:
0.109
Gnomad ASJ
AF:
0.0764
Gnomad EAS
AF:
0.202
Gnomad SAS
AF:
0.0977
Gnomad FIN
AF:
0.105
Gnomad MID
AF:
0.0812
Gnomad NFE
AF:
0.0746
Gnomad OTH
AF:
0.0910
GnomAD3 exomes
AF:
0.111
AC:
21102
AN:
189860
Hom.:
1385
AF XY:
0.106
AC XY:
10859
AN XY:
102806
show subpopulations
Gnomad AFR exome
AF:
0.164
Gnomad AMR exome
AF:
0.158
Gnomad ASJ exome
AF:
0.0763
Gnomad EAS exome
AF:
0.214
Gnomad SAS exome
AF:
0.0927
Gnomad FIN exome
AF:
0.121
Gnomad NFE exome
AF:
0.0771
Gnomad OTH exome
AF:
0.0962
GnomAD4 exome
AF:
0.0963
AC:
55075
AN:
572180
Hom.:
3168
Cov.:
6
AF XY:
0.0939
AC XY:
28869
AN XY:
307390
show subpopulations
Gnomad4 AFR exome
AF:
0.159
Gnomad4 AMR exome
AF:
0.152
Gnomad4 ASJ exome
AF:
0.0741
Gnomad4 EAS exome
AF:
0.210
Gnomad4 SAS exome
AF:
0.0893
Gnomad4 FIN exome
AF:
0.119
Gnomad4 NFE exome
AF:
0.0750
Gnomad4 OTH exome
AF:
0.0967
GnomAD4 genome
AF:
0.104
AC:
14219
AN:
136544
Hom.:
798
Cov.:
19
AF XY:
0.105
AC XY:
6890
AN XY:
65366
show subpopulations
Gnomad4 AFR
AF:
0.149
Gnomad4 AMR
AF:
0.109
Gnomad4 ASJ
AF:
0.0764
Gnomad4 EAS
AF:
0.201
Gnomad4 SAS
AF:
0.0957
Gnomad4 FIN
AF:
0.105
Gnomad4 NFE
AF:
0.0747
Gnomad4 OTH
AF:
0.0933
Alfa
AF:
0.0913
Hom.:
113
Bravo
AF:
0.116

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxMay 12, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.88
Cadd
Benign
11
Dann
Benign
0.62

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.

Other links and lift over

dbSNP: rs8177953; hg19: chr16-81116383; COSMIC: COSV59602167; COSMIC: COSV59602167; API