NM_013392.4:c.934C>T

Variant names:

• chr2-27439796-C-T
• NM_013392.4:c.934C>T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_013392.4(NRBP1):​c.934C>T​(p.Pro312Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: NRBP1 NM_013392.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.08
• Publications: 0 publications found

Genes affected

NRBP1 (HGNC:7993): (nuclear receptor binding protein 1) Predicted to enable protein homodimerization activity. Involved in endoplasmic reticulum to Golgi vesicle-mediated transport. Located in endomembrane system. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.902

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013392.4. 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
	NRBP1	NM_013392.4	MANE Select	c.934C>T	p.Pro312Ser	missense	Exon 11 of 18	NP_037524.1	Q9UHY1
	NRBP1	NM_001321358.2		c.958C>T	p.Pro320Ser	missense	Exon 12 of 19	NP_001308287.1	F8W6G1
	NRBP1	NM_001321359.2		c.958C>T	p.Pro320Ser	missense	Exon 12 of 19	NP_001308288.1	F8W6G1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRBP1	ENST00000379852.8	TSL:1 MANE Select	c.934C>T	p.Pro312Ser	missense	Exon 11 of 18	ENSP00000369181.3	Q9UHY1
	NRBP1	ENST00000379863.7	TSL:5	c.958C>T	p.Pro320Ser	missense	Exon 12 of 19	ENSP00000369192.3	F8W6G1
	NRBP1	ENST00000857545.1		c.958C>T	p.Pro320Ser	missense	Exon 12 of 19	ENSP00000527604.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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	Uncertain	0.34
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.16
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.67	D
Eigen	Pathogenic	0.75
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.89	D
M_CAP	Pathogenic	0.30	D
MetaRNN	Pathogenic	0.90	D
MetaSVM	Uncertain	0.46	D
MutationAssessor	Pathogenic	3.1	M
PhyloP100		6.1
PrimateAI	Uncertain	0.57	T
PROVEAN	Pathogenic	-5.7	D
REVEL	Pathogenic	0.75
Sift	Uncertain	0.026	D
Sift4G	Uncertain	0.014	D
Polyphen		0.88	P
Vest4		0.76
MutPred		0.68		Gain of phosphorylation at P320 (P = 0.033)
MVP		0.84
MPC		1.1
ClinPred		0.99	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.51
gMVP		0.88
Mutation Taster		=23/77	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

hg19: chr2-27662663;