8-28048371-A-T

Variant names:

• chr8-28048371-A-T
• rs6983473
• NM_001010906.2:c.1207-759T>A

Variant summary

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

The NM_001010906.2(NUGGC):​c.1207-759T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.272 in 152,044 control chromosomes in the GnomAD database, including 5,919 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.27 (5919 hom., cov: 31)
• Consequence: NUGGC NM_001010906.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.721
• Publications: 5 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 (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.435 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001010906.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUGGC	NM_001010906.2	MANE Select	c.1207-759T>A		intron	N/A	NP_001010906.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUGGC	ENST00000413272.7	TSL:5 MANE Select	c.1207-759T>A		intron	N/A	ENSP00000408697.2
	NUGGC	ENST00000952401.1		c.1117-759T>A		intron	N/A	ENSP00000622460.1
	NUGGC	ENST00000952402.1		c.976-759T>A		intron	N/A	ENSP00000622461.1

Frequencies

GnomAD3 genomes AF: 0.272 AC: 41253 AN: 151926 Hom.: 5899 Cov.: 31

Gnomad AFR AF: 0.297

Gnomad AMI AF: 0.129

Gnomad AMR AF: 0.361

Gnomad ASJ AF: 0.223

Gnomad EAS AF: 0.451

Gnomad SAS AF: 0.309

Gnomad FIN AF: 0.246

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.255

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.272 AC: 41316 AN: 152044 Hom.: 5919 Cov.: 31 AF XY: 0.277 AC XY: 20551 AN XY: 74312

African (AFR) AF: 0.297 AC: 12315 AN: 41478

American (AMR) AF: 0.361 AC: 5514 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.223 AC: 774 AN: 3470

East Asian (EAS) AF: 0.451 AC: 2333 AN: 5176

South Asian (SAS) AF: 0.308 AC: 1481 AN: 4810

European-Finnish (FIN) AF: 0.246 AC: 2591 AN: 10538

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.229 AC: 15571 AN: 67988

Other (OTH) AF: 0.261 AC: 550 AN: 2104

Alfa AF: 0.245 Hom.: 585

Bravo AF: 0.284

Asia WGS AF: 0.385 AC: 1337 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	11
DANN	Benign	0.82
PhyloP100		0.72
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: rs6983473; hg19: chr8-27905888;