11-17330136-C-T

Variant names:

• chr11-17330136-C-T
• rs757081
• NM_005013.4:c.1012C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_005013.4(NUCB2):​c.1012C>T​(p.Gln338*) variant causes a stop gained change. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NUCB2 NM_005013.4 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.26
• Publications: 0 publications found

Genes affected

NUCB2 (HGNC:8044): (nucleobindin 2) This gene encodes a protein with a suggested role in calcium level maintenance, eating regulation in the hypothalamus, and release of tumor necrosis factor from vascular endothelial cells. This protein binds calcium and has EF-folding domains. [provided by RefSeq, Oct 2011]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005013.4. 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
	NUCB2	NM_005013.4	MANE Select	c.1012C>T	p.Gln338*	stop_gained	Exon 12 of 14	NP_005004.1
	NUCB2	NM_001352661.2		c.1015C>T	p.Gln339*	stop_gained	Exon 14 of 16	NP_001339590.1
	NUCB2	NM_001352663.2		c.1015C>T	p.Gln339*	stop_gained	Exon 13 of 15	NP_001339592.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUCB2	ENST00000529010.6	TSL:1 MANE Select	c.1012C>T	p.Gln338*	stop_gained	Exon 12 of 14	ENSP00000436455.1
	NUCB2	ENST00000646648.1		n.*324C>T		non_coding_transcript_exon	Exon 14 of 17	ENSP00000495210.1
	NUCB2	ENST00000646648.1		n.*324C>T		3_prime_UTR	Exon 14 of 17	ENSP00000495210.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 151732 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1321728 Hom.: 0 Cov.: 20 AF XY: 0.00 AC XY: 0 AN XY: 658458

African (AFR) AF: 0.00 AC: 0 AN: 30496

American (AMR) AF: 0.00 AC: 0 AN: 34212

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23720

East Asian (EAS) AF: 0.00 AC: 0 AN: 38410

South Asian (SAS) AF: 0.00 AC: 0 AN: 75050

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51746

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5246

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1007608

Other (OTH) AF: 0.00 AC: 0 AN: 55240

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 151732 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74088

African (AFR) AF: 0.00 AC: 0 AN: 41300

American (AMR) AF: 0.00 AC: 0 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10490

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67936

Other (OTH) AF: 0.00 AC: 0 AN: 2086

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.62	D
BayesDel_noAF	Pathogenic	0.65
CADD	Pathogenic	40
DANN	Uncertain	1.0
Eigen	Pathogenic	1.1
Eigen_PC	Pathogenic	0.97
FATHMM_MKL	Uncertain	0.95	D
PhyloP100		4.3
Vest4		0.80
ClinPred		1.0	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=16/184	disease causing (fs/PTC)

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: rs757081; hg19: chr11-17351683;