10-63153794-A-T

Variant names:

• chr10-63153794-A-T
• NM_030759.5:c.440A>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_030759.5(NRBF2):​c.440A>T​(p.Gln147Leu) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: NRBF2 NM_030759.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.48

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17250124).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRBF2	NM_030759.5	c.440A>T	p.Gln147Leu	missense_variant	Exon 4 of 4	ENST00000277746.11	NP_110386.2
NRBF2	NM_001282405.2	c.410A>T	p.Gln137Leu	missense_variant	Exon 3 of 3		NP_001269334.1
NRBF2	XM_047425132.1	c.308A>T	p.Gln103Leu	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.440A>T	p.Gln147Leu	missense_variant	Exon 4 of 4	1	NM_030759.5	ENSP00000277746.6
NRBF2	ENST00000435510.6	c.410A>T	p.Gln137Leu	missense_variant	Exon 3 of 3	2		ENSP00000397502.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 31, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.440A>T (p.Q147L) alteration is located in exon 4 (coding exon 4) of the NRBF2 gene. This alteration results from a A to T substitution at nucleotide position 440, causing the glutamine (Q) at amino acid position 147 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.081	.;T
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.89	D;D
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.17	T;T
MetaSVM	Benign	-0.68	T
MutationAssessor	Uncertain	2.1	.;M
PrimateAI	Benign	0.34	T
PROVEAN	Uncertain	-3.8	D;N
REVEL	Benign	0.20
Sift	Uncertain	0.021	D;T
Sift4G	Uncertain	0.045	D;T
Polyphen		0.53	.;P
Vest4		0.16
MutPred		0.49		.;Loss of methylation at K148 (P = 0.0317);
MVP		0.82
MPC		0.35
ClinPred		0.93	D
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.098
gMVP		0.14

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: chr10-64913554;