10-63154175-T-G

Variant names:

• chr10-63154175-T-G
• rs148024249
• NM_030759.5:c.821T>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_030759.5(NRBF2):​c.821T>G​(p.Met274Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,457,212 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. M274T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: NRBF2 NM_030759.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.07
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37174767).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRBF2	NM_030759.5	c.821T>G	p.Met274Arg	missense_variant	Exon 4 of 4	ENST00000277746.11	NP_110386.2
NRBF2	NM_001282405.2	c.791T>G	p.Met264Arg	missense_variant	Exon 3 of 3		NP_001269334.1
NRBF2	XM_047425132.1	c.689T>G	p.Met230Arg	missense_variant	Exon 3 of 3		XP_047281088.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRBF2	ENST00000277746.11	c.821T>G	p.Met274Arg	missense_variant	Exon 4 of 4	1	NM_030759.5	ENSP00000277746.6
NRBF2	ENST00000435510.6	c.791T>G	p.Met264Arg	missense_variant	Exon 3 of 3	2		ENSP00000397502.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1457212 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 725214

African (AFR) AF: 0.00 AC: 0 AN: 33378

American (AMR) AF: 0.00 AC: 0 AN: 44604

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26060

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39684

South Asian (SAS) AF: 0.00 AC: 0 AN: 86094

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53188

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 9.02e-7 AC: 1 AN: 1108216

Other (OTH) AF: 0.00 AC: 0 AN: 60230

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.48
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.060
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.083	.;T
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.74	T;T
M_CAP	Benign	0.042	D
MetaRNN	Benign	0.37	T;T
MetaSVM	Benign	-0.55	T
MutationAssessor	Benign	1.9	.;M
PhyloP100		7.1
PrimateAI	Uncertain	0.55	T
PROVEAN	Uncertain	-3.0	D;N
REVEL	Uncertain	0.50
Sift	Uncertain	0.0020	D;D
Sift4G	Uncertain	0.0040	D;D
Polyphen		0.71	.;P
Vest4		0.40
MutPred		0.56		.;Gain of solvent accessibility (P = 0.0105);
MVP		0.86
MPC		0.63
ClinPred		0.95	D
GERP RS		5.6
Varity_R		0.83
gMVP		0.41
Mutation Taster		=37/63	disease causing

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: rs148024249; hg19: chr10-64913935;