rs7817227

Positions:

• chr8-28060540-T-A
• chr8-28060540-T-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.983A>T​(p.Gln328Leu) 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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q328R) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000021 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NUGGC NM_001010906.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.525

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=0.13677788).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NUGGC	NM_001010906.2	c.983A>T	p.Gln328Leu	missense_variant	8/19	ENST00000413272.7	NP_001010906.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NUGGC	ENST00000413272.7	c.983A>T	p.Gln328Leu	missense_variant	8/19	5	NM_001010906.2	ENSP00000408697.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.0000121 AC: 3 AN: 248906 Hom.: 0 AF XY: 0.0000148 AC XY: 2 AN XY: 135040

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.0000994

Gnomad EAS exome AF: 0.0000557

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000886

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000205 AC: 3 AN: 1461522 Hom.: 0 Cov.: 47 AF XY: 0.00000275 AC XY: 2 AN XY: 727036

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

Alfa AF: 0.00000420 Hom.: 117426

ExAC AF: 0.00000828 AC: 1

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	14
DANN	Benign	0.93
DEOGEN2	Benign	0.036	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.34	T
M_CAP	Benign	0.037	D
MetaRNN	Benign	0.14	T
MetaSVM	Uncertain	-0.057	T
MutationAssessor	Benign	0.0	N
PrimateAI	Benign	0.33	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.24
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.032	D
Polyphen		0.0010	B
Vest4		0.26
MutPred		0.50		Gain of helix (P = 0.0425);
MVP		0.30
MPC		0.085
ClinPred		0.057	T
GERP RS		1.3
Varity_R		0.16
gMVP		0.38

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

LitVar

Other links and lift over

dbSNP: rs7817227; hg19: chr8-27918057;