rs61734185

Variant names:

• chr7-151345361-G-C
• rs61734185
• NM_001243351.2:c.12G>C

Your query was ambiguous. Multiple possible variants found:

• chr7-151345361-G-C
• chr7-151345361-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001243351.2(NUB1):​c.12G>C​(p.Lys4Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Benign in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NUB1 NM_001243351.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.60
• Publications: 10 publications found

Genes affected

NUB1 (HGNC:17623): (negative regulator of ubiquitin like proteins 1) This gene encodes a protein that functions as a negative regulator of NEDD8, a ubiquitin-like protein that conjugates with cullin family members in order to regulate vital biological events. The protein encoded by this gene regulates the NEDD8 conjugation system post-transcriptionally by recruiting NEDD8 and its conjugates to the proteasome for degradation. This protein interacts with the product of the AIPL1 gene, which is associated with Leber congenital amaurosis, an inherited retinopathy, and mutations in that gene can abolish interaction with this protein, which may contribute to the pathogenesis. This protein is also known to accumulate in Lewy bodies in Parkinson's disease and dementia with Lewy bodies, and in glial cytoplasmic inclusions in multiple system atrophy, with this abnormal accumulation being specific to alpha-synucleinopathy lesions. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Aug 2011]

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24733219).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUB1	NM_001243351.2	c.12G>C	p.Lys4Asn	missense_variant	Exon 2 of 15	ENST00000568733.6	NP_001230280.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUB1	ENST00000568733.6	c.12G>C	p.Lys4Asn	missense_variant	Exon 2 of 15	1	NM_001243351.2	ENSP00000454264.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0067	T;T;T;T
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.81	T;T;T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.25	T;T;T;T
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	1.9	.;.;L;.
PhyloP100		3.6
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-0.21	N;N;N;N
REVEL	Benign	0.11
Sift	Uncertain	0.010	D;D;D;D
Sift4G	Benign	0.29	T;T;D;D
Polyphen		0.94	.;.;P;.
Vest4		0.54
MutPred		0.24		.;.;Loss of MoRF binding (P = 0.0224);Loss of MoRF binding (P = 0.0224);
MVP		0.50
MPC		0.50
ClinPred		0.80	D
GERP RS		5.6
PromoterAI		0.019	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.13
gMVP		0.18
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs61734185; hg19: chr7-151042447;