1-84501855-G-T

Variant names:

• chr1-84501855-G-T
• NM_005274.3:c.197C>A

Variant summary

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

The NM_005274.3(GNG5):​c.197C>A​(p.Ser66Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GNG5 NM_005274.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.66

Genes affected

GNG5 (HGNC:4408): (G protein subunit gamma 5) G proteins are trimeric (alpha-beta-gamma) membrane-associated proteins that regulate flow of information from cell surface receptors to a variety of internal metabolic effectors. Interaction of a G protein with its activated receptor promotes exchange of GTP for GDP that is bound to the alpha subunit. The alpha-GTP complex dissociates from the beta-gamma heterodimer so that the subunits, in turn, may interact with and regulate effector molecules (Gilman, 1987 [PubMed 3113327]; summary by Ahmad et al., 1995) [PubMed 7606925].[supplied by OMIM, Nov 2010]

ENSG00000285851 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GNG5	NM_005274.3	c.197C>A	p.Ser66Tyr	missense_variant	Exon 3 of 4	ENST00000370645.9	NP_005265.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GNG5	ENST00000370645.9	c.197C>A	p.Ser66Tyr	missense_variant	Exon 3 of 4	2	NM_005274.3	ENSP00000359679.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 08, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.197C>A (p.S66Y) alteration is located in exon 3 (coding exon 2) of the GNG5 gene. This alteration results from a C to A substitution at nucleotide position 197, causing the serine (S) at amino acid position 66 to be replaced by a tyrosine (Y). 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	Uncertain	0.43
BayesDel_addAF	Uncertain	0.055	T
BayesDel_noAF	Benign	-0.16
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	T;T
Eigen	Uncertain	0.65
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.92	.;D
M_CAP	Benign	0.043	D
MetaRNN	Uncertain	0.51	D;D
MetaSVM	Benign	-1.1	T
PrimateAI	Pathogenic	0.82	D
PROVEAN	Uncertain	-2.5	D;D
REVEL	Benign	0.23
Sift	Uncertain	0.017	D;D
Sift4G	Benign	0.69	T;T
Polyphen		0.77	P;P
Vest4		0.62
MutPred		0.39		Loss of disorder (P = 1e-04);Loss of disorder (P = 1e-04);
MVP		0.23
MPC		1.3
ClinPred		0.97	D
GERP RS		5.6
Varity_R		0.49
gMVP		0.64

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: chr1-84967538;