Genetic Variant GHDC:p.Gly329Ser (chr17-42191115-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 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. 15/21 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

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.87

Publications

0 publications found

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]

GHDC links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.21091259).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032484.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GHDC	NM_032484.5	MANE Select	c.985G>A	p.Gly329Ser	missense	Exon 6 of 10	NP_115873.1	Q8N2G8-1
	GHDC	NM_001142623.2		c.985G>A	p.Gly329Ser	missense	Exon 6 of 10	NP_001136095.1	Q8N2G8-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GHDC	ENST00000587427.6	TSL:1 MANE Select	c.985G>A	p.Gly329Ser	missense	Exon 6 of 10	ENSP00000467585.1	Q8N2G8-1
GHDC	ENST00000301671.12	TSL:2	c.985G>A	p.Gly329Ser	missense	Exon 5 of 9	ENSP00000301671.7	Q8N2G8-1
GHDC	ENST00000853517.1		c.985G>A	p.Gly329Ser	missense	Exon 6 of 10	ENSP00000523576.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000496

AC:

AN:

201768

AF XY:

0.00000914

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.08e-7

AC:

AN:

1412488

Hom.:

Cov.:

AF XY:

0.00000143

AC XY:

AN XY:

700006

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31092

American (AMR)

AF:

0.0000299

AC:

AN:

33428

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23006

East Asian (EAS)

AF:

0.00

AC:

AN:

38606

South Asian (SAS)

AF:

0.00

AC:

AN:

78848

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52222

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5552

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1091736

Other (OTH)

AF:

0.00

AC:

AN:

57998

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0061

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.40

FATHMM_MKL

Benign

0.080

LIST_S2

Benign

0.74

M_CAP

Benign

0.0061

MetaRNN

Benign

0.21

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

PhyloP100

1.9

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.50

REVEL

Benign

0.096

Sift

Benign

0.31

Sift4G

Benign

0.065

Polyphen

0.96

Vest4

0.33

MutPred

0.69

Gain of glycosylation at G329 (P = 0.0401)

MVP

0.37

MPC

0.67

ClinPred

0.27

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

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over