rs370940556

Variant names:

• chr7-151376697-G-A
• rs370940556
• NM_001243351.2:c.1555G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-151376697-G-A
• chr7-151376697-G-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001243351.2(NUB1):​c.1555G>A​(p.Val519Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000261 in 1,609,950 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. V519F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000099 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000019 (0 hom.)
• Consequence: NUB1 NM_001243351.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.28
• Publications: 0 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]

WDR86 (HGNC:28020): (WD repeat domain 86)

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.059164196).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUB1	NM_001243351.2	c.1555G>A	p.Val519Ile	missense_variant	Exon 14 of 15	ENST00000568733.6	NP_001230280.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUB1	ENST00000568733.6	c.1555G>A	p.Val519Ile	missense_variant	Exon 14 of 15	1	NM_001243351.2	ENSP00000454264.2

Frequencies

GnomAD3 genomes AF: 0.0000986 AC: 15 AN: 152122 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000290

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: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000290 AC: 7 AN: 241314 AF XY: 0.00

Gnomad AFR exome AF: 0.000341

Gnomad AMR exome AF: 0.0000296

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000170

GnomAD4 exome AF: 0.0000185 AC: 27 AN: 1457828 Hom.: 0 Cov.: 31 AF XY: 0.0000221 AC XY: 16 AN XY: 724876

African (AFR) AF: 0.000179 AC: 6 AN: 33442

American (AMR) AF: 0.00 AC: 0 AN: 44248

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26052

East Asian (EAS) AF: 0.00 AC: 0 AN: 39536

South Asian (SAS) AF: 0.0000234 AC: 2 AN: 85440

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52634

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 0.0000126 AC: 14 AN: 1110466

Other (OTH) AF: 0.0000830 AC: 5 AN: 60254

GnomAD4 genome AF: 0.0000986 AC: 15 AN: 152122 Hom.: 0 Cov.: 33 AF XY: 0.000121 AC XY: 9 AN XY: 74312

African (AFR) AF: 0.000290 AC: 12 AN: 41394

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.000188 AC: 2 AN: 10614

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000875 Hom.: 0

Bravo AF: 0.0000869

ESP6500AA AF: 0.000462 AC: 2

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000495 AC: 6

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0043	T;T;T
Eigen	Benign	-0.096
Eigen_PC	Benign	0.099
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.77	T;T;T
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.059	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	.;.;L
PhyloP100		2.3
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.20	N;N;.
REVEL	Benign	0.066
Sift	Benign	0.18	T;T;.
Sift4G	Benign	0.19	T;T;.
Polyphen		0.048	.;.;B
Vest4		0.13
MVP		0.21
MPC		0.23
ClinPred		0.039	T
GERP RS		5.6
Varity_R		0.027
gMVP		0.45
Mutation Taster		=93/7	polymorphism

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: rs370940556; hg19: chr7-151073783;