chr8-28029389-G-C

Position:

• chr8-28029389-G-C

Variant summary

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

The NM_001010906.2(NUGGC):​c.2031C>G​(p.Ile677Met) 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. 14/21 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)
• Consequence: NUGGC NM_001010906.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.792

Genes affected

NUGGC (HGNC:33550): (nuclear GTPase, germinal center associated) Enables GTPase activity. Involved in cellular response to lipopolysaccharide; negative regulation of apoptotic process; and regulation of nuclear cell cycle DNA replication. Predicted to be located in nucleus. [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=0.16110623).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NUGGC	NM_001010906.2	c.2031C>G	p.Ile677Met	missense_variant	17/19	ENST00000413272.7	NP_001010906.1
NUGGC	XM_011544523.3	c.2103C>G	p.Ile701Met	missense_variant	17/19		XP_011542825.1
NUGGC	XM_011544524.4	c.2103C>G	p.Ile701Met	missense_variant	17/19		XP_011542826.1
NUGGC	XM_011544525.2	c.870C>G	p.Ile290Met	missense_variant	9/11		XP_011542827.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NUGGC	ENST00000413272.7	c.2031C>G	p.Ile677Met	missense_variant	17/19	5	NM_001010906.2	ENSP00000408697	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

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

May 04, 2022

The c.2031C>G (p.I677M) alteration is located in exon 17 (coding exon 16) of the NUGGC gene. This alteration results from a C to G substitution at nucleotide position 2031, causing the isoleucine (I) at amino acid position 677 to be replaced by a methionine (M). 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	0.14
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	19
DANN	Benign	0.97
DEOGEN2	Benign	0.0036	T
Eigen	Benign	-0.068
Eigen_PC	Benign	0.10
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.0059	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L
MutationTaster	Benign	0.51	N;N
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-0.37	N
REVEL	Benign	0.040
Sift	Benign	0.12	T
Sift4G	Benign	0.18	T
Polyphen		0.28	B
Vest4		0.42
MutPred		0.29		Loss of catalytic residue at I677 (P = 0.0235);
MVP		0.14
MPC		0.16
ClinPred		0.45	T
GERP RS		4.6
Varity_R		0.10
gMVP		0.15

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: chr8-27886906;