rs4979032

Variant names:

• chr9-111664695-G-A
• rs4979032
• NM_001017998.4:c.82-2120G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001017998.4(GNG10):​c.82-2120G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.381 in 151,840 control chromosomes in the GnomAD database, including 11,916 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.38 (11916 hom., cov: 30)
• Consequence: GNG10 NM_001017998.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.466
• Publications: 6 publications found

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:37501): (DNAJC25-GNG10 readthrough) This gene represents naturally-occurring mRNAs that are co-transcribed products of the neighboring DNAJC25 and GNG10 genes. These transcripts include the first exon of DNAJC25 and the last two exons of GNG10, resulting in a protein that combines the N-terminus of DNAJC25 and the C-terminus of GNG10. [provided by RefSeq, Dec 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.53 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GNG10	NM_001017998.4	c.82-2120G>A		intron_variant	Intron 1 of 2	ENST00000374293.5	NP_001017998.1
DNAJC25-GNG10	NM_004125.4	c.337-2120G>A		intron_variant	Intron 1 of 2		NP_004116.2
GNG10	NM_001198664.2	c.82-2120G>A		intron_variant	Intron 1 of 2		NP_001185593.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GNG10	ENST00000374293.5	c.82-2120G>A		intron_variant	Intron 1 of 2	1	NM_001017998.4	ENSP00000363411.3
DNAJC25-GNG10	ENST00000374294.3	c.337-2120G>A		intron_variant	Intron 1 of 2	2		ENSP00000363412.3

Frequencies

GnomAD3 genomes AF: 0.380 AC: 57695 AN: 151722 Hom.: 11884 Cov.: 30

Gnomad AFR AF: 0.536

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.448

Gnomad ASJ AF: 0.374

Gnomad EAS AF: 0.437

Gnomad SAS AF: 0.309

Gnomad FIN AF: 0.317

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.285

Gnomad OTH AF: 0.365

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.381 AC: 57780 AN: 151840 Hom.: 11916 Cov.: 30 AF XY: 0.384 AC XY: 28487 AN XY: 74224

African (AFR) AF: 0.536 AC: 22181 AN: 41366

American (AMR) AF: 0.449 AC: 6845 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.374 AC: 1300 AN: 3472

East Asian (EAS) AF: 0.437 AC: 2249 AN: 5148

South Asian (SAS) AF: 0.308 AC: 1487 AN: 4822

European-Finnish (FIN) AF: 0.317 AC: 3338 AN: 10520

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.285 AC: 19332 AN: 67942

Other (OTH) AF: 0.361 AC: 759 AN: 2104

Alfa AF: 0.312 Hom.: 4095

Bravo AF: 0.400

Asia WGS AF: 0.372 AC: 1291 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.5
DANN	Benign	0.72
PhyloP100		-0.47
Mutation Taster		=100/0	polymorphism (auto)

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: rs4979032; hg19: chr9-114426975; COSMIC: COSV65349757;