17-42190720-C-G

Variant names:

• chr17-42190720-C-G
• rs1465765316
• NM_032484.5:c.1192G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032484.5(GHDC):​c.1192G>C​(p.Gly398Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. 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. G398S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GHDC NM_032484.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.102
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14174327).

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.1192G>C	p.Gly398Arg	missense	Exon 8 of 10	NP_115873.1	Q8N2G8-1
	GHDC	NM_001142623.2		c.1192G>C	p.Gly398Arg	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.1192G>C	p.Gly398Arg	missense	Exon 8 of 10	ENSP00000467585.1	Q8N2G8-1
	GHDC	ENST00000301671.12	TSL:2	c.1192G>C	p.Gly398Arg	missense	Exon 7 of 9	ENSP00000301671.7	Q8N2G8-1
	GHDC	ENST00000853517.1		c.1192G>C	p.Gly398Arg	missense	Exon 8 of 10	ENSP00000523576.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	4.5
DANN	Benign	0.89
DEOGEN2	Benign	0.019	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.036	N
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.92	L
PhyloP100		0.10
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.030
Sift	Benign	0.25	T
Sift4G	Benign	0.41	T
Polyphen		0.0030	B
Vest4		0.18
MutPred		0.28		Gain of solvent accessibility (P = 0.0674)
MVP		0.030
MPC		0.21
ClinPred		0.027	T
GERP RS		-2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.054
gMVP		0.48
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs1465765316; hg19: chr17-40342738;