10-63154204-T-A

Variant names:

• chr10-63154204-T-A
• rs1369466505
• NM_030759.5:c.850T>A

Variant summary

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

The NM_030759.5(NRBF2):​c.850T>A​(p.Phe284Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000162 in 1,418,808 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000016 (0 hom.)
• Consequence: NRBF2 NM_030759.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.775
• Publications: 0 publications found

Genes affected

NRBF2 (HGNC:19692): (nuclear receptor binding factor 2) Involved in autophagy. Located in cytoplasm. Colocalizes with phosphatidylinositol 3-kinase complex, class III. [provided by Alliance of Genome Resources, Apr 2022]

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=0.0929327).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030759.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRBF2	NM_030759.5	MANE Select	c.850T>A	p.Phe284Ile	missense	Exon 4 of 4	NP_110386.2	Q96F24-1
	NRBF2	NM_001282405.2		c.820T>A	p.Phe274Ile	missense	Exon 3 of 3	NP_001269334.1	Q96F24-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRBF2	ENST00000277746.11	TSL:1 MANE Select	c.850T>A	p.Phe284Ile	missense	Exon 4 of 4	ENSP00000277746.6	Q96F24-1
	NRBF2	ENST00000963003.1		c.973T>A	p.Phe325Ile	missense	Exon 5 of 5	ENSP00000633062.1
	NRBF2	ENST00000857328.1		c.946T>A	p.Phe316Ile	missense	Exon 5 of 5	ENSP00000527387.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000162 AC: 23 AN: 1418808 Hom.: 0 Cov.: 24 AF XY: 0.0000184 AC XY: 13 AN XY: 705550

African (AFR) AF: 0.00 AC: 0 AN: 31954

American (AMR) AF: 0.00 AC: 0 AN: 40432

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25078

East Asian (EAS) AF: 0.00 AC: 0 AN: 39316

South Asian (SAS) AF: 0.00 AC: 0 AN: 82904

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52504

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5630

European-Non Finnish (NFE) AF: 0.0000203 AC: 22 AN: 1082248

Other (OTH) AF: 0.0000170 AC: 1 AN: 58742

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	16
DANN	Benign	0.91
DEOGEN2	Benign	0.056	T
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.64
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.0099	T
MetaRNN	Benign	0.093	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PhyloP100		0.78
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.44	N
REVEL	Benign	0.037
Sift	Benign	0.051	T
Sift4G	Benign	0.12	T
Polyphen		0.053	B
Vest4		0.25
MutPred		0.41		Loss of ubiquitination at K282 (P = 0.0937)
MVP		0.30
MPC		0.25
ClinPred		0.18	T
GERP RS		-3.3
Varity_R		0.042
gMVP		0.13
Mutation Taster		=87/13	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: rs1369466505; hg19: chr10-64913964;