2-27439796-C-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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

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

Verdict is Uncertain_significance. Variant got 4 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRBP1	NM_013392.4	c.934C>T	p.Pro312Ser	missense_variant	Exon 11 of 18	ENST00000379852.8	NP_037524.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRBP1	ENST00000379852.8	c.934C>T	p.Pro312Ser	missense_variant	Exon 11 of 18	1	NM_013392.4	ENSP00000369181.3
NRBP1	ENST00000379863.7	c.958C>T	p.Pro320Ser	missense_variant	Exon 12 of 19	5		ENSP00000369192.3
NRBP1	ENST00000233557.7	c.934C>T	p.Pro312Ser	missense_variant	Exon 12 of 19	2		ENSP00000233557.3
NRBP1	ENST00000460499.5	n.1444C>T		non_coding_transcript_exon_variant	Exon 4 of 11	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 19, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.934C>T (p.P312S) alteration is located in exon 11 (coding exon 10) of the NRBP1 gene. This alteration results from a C to T substitution at nucleotide position 934, causing the proline (P) at amino acid position 312 to be replaced by a serine (S). 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	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;D;D
Eigen	Pathogenic	0.75
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.89	.;D;D
M_CAP	Pathogenic	0.30	D
MetaRNN	Pathogenic	0.90	D;D;D
MetaSVM	Uncertain	0.46	D
MutationAssessor	Pathogenic	3.1	M;M;.
PrimateAI	Uncertain	0.57	T
PROVEAN	Pathogenic	-5.7	D;D;D
REVEL	Pathogenic	0.75
Sift	Uncertain	0.026	D;D;D
Sift4G	Uncertain	0.014	D;D;D
Polyphen		0.88	P;P;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

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: chr2-27662663;