9-111661682-G-C

Position:

• chr9-111661682-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001017998.4(GNG10):​c.48G>C​(p.Gln16His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 8.1e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GNG10 NM_001017998.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.20

Genes affected

GNG10 (HGNC:4402): (G protein subunit gamma 10) Predicted to enable G-protein beta-subunit binding activity. Predicted to be involved in G protein-coupled receptor signaling pathway. Predicted to be located in plasma membrane. Predicted to be part of heterotrimeric G-protein complex. [provided by Alliance of Genome Resources, Apr 2022]

DNAJC25-GNG10 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.785

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GNG10	NM_001017998.4	c.48G>C	p.Gln16His	missense_variant	1/3	ENST00000374293.5
DNAJC25-GNG10	NM_004125.4	c.337-5133G>C		intron_variant
GNG10	NM_001198664.2	c.48G>C	p.Gln16His	missense_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GNG10	ENST00000374293.5	c.48G>C	p.Gln16His	missense_variant	1/3	1	NM_001017998.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 8.10e-7 AC: 1 AN: 1235248 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 611206

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 0.00000102

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 28, 2023

The c.48G>C (p.Q16H) alteration is located in exon 1 (coding exon 1) of the GNG10 gene. This alteration results from a G to C substitution at nucleotide position 48, causing the glutamine (Q) at amino acid position 16 to be replaced by a histidine (H). 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	Pathogenic	0.94
BayesDel_addAF	Benign	-0.032	T
BayesDel_noAF	Benign	-0.28
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.22	T
Eigen	Benign	-0.082
Eigen_PC	Benign	-0.13
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Pathogenic	0.93	D
MetaRNN	Pathogenic	0.78	D
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	D;D;D
PROVEAN	Pathogenic	-4.6	D
REVEL	Benign	0.27
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		0.77	P
Vest4		0.47
MutPred		0.80		Loss of disorder (P = 0.052);
MVP		0.16
MPC		1.4
ClinPred		0.98	D
GERP RS		3.0
Varity_R		0.70
gMVP		0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-114423962;