17-42190734-C-A

Variant names:

• chr17-42190734-C-A
• rs752186887
• NM_032484.5:c.1178G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_032484.5(GHDC):​c.1178G>T​(p.Arg393Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,806 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R393Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: GHDC NM_032484.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.14
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.1178G>T	p.Arg393Leu	missense	Exon 8 of 10	NP_115873.1	Q8N2G8-1
	GHDC	NM_001142623.2		c.1178G>T	p.Arg393Leu	missense	Exon 8 of 10	NP_001136095.1	Q8N2G8-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GHDC	ENST00000587427.6	TSL:1 MANE Select	c.1178G>T	p.Arg393Leu	missense	Exon 8 of 10	ENSP00000467585.1	Q8N2G8-1
	GHDC	ENST00000301671.12	TSL:2	c.1178G>T	p.Arg393Leu	missense	Exon 7 of 9	ENSP00000301671.7	Q8N2G8-1
	GHDC	ENST00000853517.1		c.1178G>T	p.Arg393Leu	missense	Exon 8 of 10	ENSP00000523576.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461806 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727220

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53362

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112002

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.11
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.20	T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.86	D
M_CAP	Uncertain	0.087	D
MetaRNN	Uncertain	0.74	D
MetaSVM	Benign	-0.43	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		5.1
PrimateAI	Uncertain	0.51	T
PROVEAN	Pathogenic	-5.0	D
REVEL	Uncertain	0.37
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.0060	D
Polyphen		1.0	D
Vest4		0.85
MutPred		0.60		Loss of disorder (P = 0.0502)
MVP		0.20
MPC		0.78
ClinPred		0.99	D
GERP RS		4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.45
gMVP		0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs752186887; hg19: chr17-40342752;