rs757081

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr11-17330136-C-A
• chr11-17330136-C-G
• chr11-17330136-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_005013.4(NUCB2):​c.1012C>A​(p.Gln338Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000000757 in 1,321,730 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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. Q338E) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.6e-7 (0 hom.)
• Consequence: NUCB2 NM_005013.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.26

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34310418).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUCB2	NM_005013.4	c.1012C>A	p.Gln338Lys	missense_variant	Exon 12 of 14	ENST00000529010.6	NP_005004.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUCB2	ENST00000529010.6	c.1012C>A	p.Gln338Lys	missense_variant	Exon 12 of 14	1	NM_005013.4	ENSP00000436455.1
NUCB2	ENST00000646648.1	n.*324C>A		non_coding_transcript_exon_variant	Exon 14 of 17			ENSP00000495210.1
NUCB2	ENST00000646648.1	n.*324C>A		3_prime_UTR_variant	Exon 14 of 17			ENSP00000495210.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.57e-7 AC: 1 AN: 1321730 Hom.: 0 Cov.: 20 AF XY: 0.00 AC XY: 0 AN XY: 658460

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000133

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.15	.;T;T;T
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.88	D;.;D;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.34	T;T;T;T
MetaSVM	Uncertain	-0.16	T
MutationAssessor	Benign	1.7	L;L;L;.
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.5	N;N;.;N
REVEL	Benign	0.079
Sift	Benign	0.19	T;T;.;T
Sift4G	Benign	0.41	T;T;T;T
Polyphen		0.10	.;B;B;.
Vest4		0.28
MutPred		0.27		Gain of ubiquitination at Q338 (P = 0.0051);Gain of ubiquitination at Q338 (P = 0.0051);Gain of ubiquitination at Q338 (P = 0.0051);.;
MVP		0.17
MPC		0.14
ClinPred		0.78	D
GERP RS		5.7
Varity_R		0.17
gMVP		0.42

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-17351683;