8-28060540-T-C

Variant names:

• chr8-28060540-T-C
• rs7817227
• NM_001010906.2:c.983A>G

Variant summary

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

The NM_001010906.2(NUGGC):​c.983A>G​(p.Gln328Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.993 in 1,613,722 control chromosomes in the GnomAD database, including 796,717 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.97 (71477 hom., cov: 31)
  • Exomes 𝑓: 1.0 (725240 hom.)
• Consequence: NUGGC NM_001010906.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.525
• Publications: 26 publications found

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

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

• BP4: Computational evidence support a benign effect (MetaRNN=1.5352871E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUGGC	NM_001010906.2	c.983A>G	p.Gln328Arg	missense_variant	Exon 8 of 19	ENST00000413272.7	NP_001010906.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUGGC	ENST00000413272.7	c.983A>G	p.Gln328Arg	missense_variant	Exon 8 of 19	5	NM_001010906.2	ENSP00000408697.2

Frequencies

GnomAD3 genomes AF: 0.968 AC: 147290 AN: 152134 Hom.: 71426 Cov.: 31

Gnomad AFR AF: 0.893

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.985

Gnomad ASJ AF: 0.988

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 1.00

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.975

GnomAD2 exomes AF: 0.991 AC: 246707 AN: 248906 AF XY: 0.993

Gnomad AFR exome AF: 0.891

Gnomad AMR exome AF: 0.993

Gnomad ASJ exome AF: 0.988

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 0.999

Gnomad OTH exome AF: 0.995

GnomAD4 exome AF: 0.996 AC: 1455726 AN: 1461470 Hom.: 725240 Cov.: 47 AF XY: 0.996 AC XY: 724464 AN XY: 727016

African (AFR) AF: 0.885 AC: 29592 AN: 33440

American (AMR) AF: 0.992 AC: 44324 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.988 AC: 25809 AN: 26132

East Asian (EAS) AF: 1.00 AC: 39690 AN: 39692

South Asian (SAS) AF: 1.00 AC: 86191 AN: 86210

European-Finnish (FIN) AF: 1.00 AC: 53400 AN: 53400

Middle Eastern (MID) AF: 0.988 AC: 5697 AN: 5768

European-Non Finnish (NFE) AF: 0.999 AC: 1111203 AN: 1111778

Other (OTH) AF: 0.991 AC: 59820 AN: 60360

GnomAD4 genome AF: 0.968 AC: 147400 AN: 152252 Hom.: 71477 Cov.: 31 AF XY: 0.970 AC XY: 72155 AN XY: 74424

African (AFR) AF: 0.893 AC: 37068 AN: 41526

American (AMR) AF: 0.985 AC: 15077 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.988 AC: 3432 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5154 AN: 5154

South Asian (SAS) AF: 1.00 AC: 4822 AN: 4824

European-Finnish (FIN) AF: 1.00 AC: 10612 AN: 10612

Middle Eastern (MID) AF: 1.00 AC: 294 AN: 294

European-Non Finnish (NFE) AF: 0.999 AC: 67968 AN: 68040

Other (OTH) AF: 0.975 AC: 2061 AN: 2114

Alfa AF: 0.992 Hom.: 128377

Bravo AF: 0.963

TwinsUK AF: 0.999 AC: 3705

ALSPAC AF: 0.999 AC: 3852

ESP6500AA AF: 0.889 AC: 3550

ESP6500EA AF: 0.999 AC: 8339

ExAC AF: 0.990 AC: 119607

Asia WGS AF: 0.993 AC: 3454 AN: 3478

EpiCase AF: 0.999

EpiControl AF: 0.999

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.049
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	2.2
DANN	Benign	0.31
DEOGEN2	Benign	0.00092	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.16	T
MetaRNN	Benign	0.0000015	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-2.1	N
PhyloP100		0.53
PrimateAI	Benign	0.33	T
PROVEAN	Benign	1.3	N
REVEL	Benign	0.22
Sift	Benign	0.63	T
Sift4G	Benign	0.82	T
Polyphen		0.0	B
Vest4		0.040
MPC		0.094
ClinPred		0.0011	T
GERP RS		1.3
Varity_R		0.042
gMVP		0.12
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: rs7817227; hg19: chr8-27918057; COSMIC: COSV107442224;