17-42191115-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_032484.5(GHDC):​c.985G>A​(p.Gly329Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000708 in 1,412,488 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

GHDC
NM_032484.5 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.87
Variant links:
Genes affected
GHDC (HGNC:24438): (GH3 domain containing) Predicted to enable acid-amino acid ligase activity. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.21091259).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GHDCNM_032484.5 linkc.985G>A p.Gly329Ser missense_variant Exon 6 of 10 ENST00000587427.6 NP_115873.1 Q8N2G8-1A0A024R1Y7
GHDCNM_001142623.2 linkc.985G>A p.Gly329Ser missense_variant Exon 6 of 10 NP_001136095.1 Q8N2G8-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GHDCENST00000587427.6 linkc.985G>A p.Gly329Ser missense_variant Exon 6 of 10 1 NM_032484.5 ENSP00000467585.1 Q8N2G8-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000496
AC:
1
AN:
201768
Hom.:
0
AF XY:
0.00000914
AC XY:
1
AN XY:
109450
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000421
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
7.08e-7
AC:
1
AN:
1412488
Hom.:
0
Cov.:
31
AF XY:
0.00000143
AC XY:
1
AN XY:
700006
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000299
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Apr 26, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.985G>A (p.G329S) alteration is located in exon 6 (coding exon 4) of the GHDC gene. This alteration results from a G to A substitution at nucleotide position 985, causing the glycine (G) at amino acid position 329 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.097
BayesDel_addAF
Benign
-0.20
T
BayesDel_noAF
Benign
-0.52
CADD
Benign
19
DANN
Uncertain
0.99
DEOGEN2
Benign
0.0061
.;T;.;T;.
Eigen
Benign
-0.33
Eigen_PC
Benign
-0.40
FATHMM_MKL
Benign
0.080
N
LIST_S2
Benign
0.74
T;.;.;T;T
M_CAP
Benign
0.0061
T
MetaRNN
Benign
0.21
T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.9
.;L;L;L;L
PrimateAI
Benign
0.32
T
PROVEAN
Benign
-0.50
.;N;N;.;.
REVEL
Benign
0.096
Sift
Benign
0.31
.;T;T;.;.
Sift4G
Benign
0.065
T;T;D;T;D
Polyphen
0.96, 0.95
.;D;P;D;P
Vest4
0.33
MutPred
0.69
Gain of glycosylation at G329 (P = 0.0401);Gain of glycosylation at G329 (P = 0.0401);Gain of glycosylation at G329 (P = 0.0401);Gain of glycosylation at G329 (P = 0.0401);Gain of glycosylation at G329 (P = 0.0401);
MVP
0.37
MPC
0.67
ClinPred
0.27
T
GERP RS
2.1
Varity_R
0.041
gMVP
0.43

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: rs1213785002; hg19: chr17-40343133; API