chr19-2520613-T-C

Variant names:

• chr19-2520613-T-C
• NM_052847.3:c.76A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_052847.3(GNG7):​c.76A>G​(p.Ile26Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/20 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: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GNG7 NM_052847.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.52

Genes affected

GNG7 (HGNC:4410): (G protein subunit gamma 7) Predicted to enable G-protein beta-subunit binding activity. Predicted to be involved in G protein-coupled receptor signaling pathway and regulation of adenylate cyclase activity. Predicted to act upstream of or within behavioral fear response; locomotory behavior; and receptor guanylyl cyclase signaling pathway. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16146642).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GNG7	NM_052847.3	c.76A>G	p.Ile26Val	missense_variant	Exon 4 of 5	ENST00000382159.8	NP_443079.1
GNG7	XM_047438629.1	c.76A>G	p.Ile26Val	missense_variant	Exon 5 of 6		XP_047294585.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GNG7	ENST00000382159.8	c.76A>G	p.Ile26Val	missense_variant	Exon 4 of 5	1	NM_052847.3	ENSP00000371594.2
GNG7	ENST00000587867.1	n.76A>G		non_coding_transcript_exon_variant	Exon 4 of 6	5		ENSP00000468650.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1388218 Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0 AN XY: 685752

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: 0.00

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

Dec 06, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.76A>G (p.I26V) alteration is located in exon 3 (coding exon 1) of the GNG7 gene. This alteration results from a A to G substitution at nucleotide position 76, causing the isoleucine (I) at amino acid position 26 to be replaced by a valine (V). 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	Benign	0.091
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	16
DANN	Benign	0.68
DEOGEN2	Benign	0.089	T
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.36
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.0049	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.1	T
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-0.13	N
REVEL	Benign	0.097
Sift	Benign	0.84	T
Sift4G	Benign	0.41	T
Polyphen		0.0010	B
Vest4		0.23
MutPred		0.45		Loss of ubiquitination at K30 (P = 0.0755);
MVP		0.24
MPC		0.22
ClinPred		0.80	D
GERP RS		3.4
Varity_R		0.052
gMVP		0.70

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-2520611;