16-22533837-C-T

Position:

• chr16-22533837-C-T

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4

The ENST00000424340.7(NPIPB5):​c.854C>T​(p.Pro285Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 10/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 4)
  • Exomes 𝑓: 0.0000045 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NPIPB5 ENST00000424340.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.904

Genes affected

NPIPB5 (HGNC:37233): (nuclear pore complex interacting protein family member B5) Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

LOC105371131 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.32567364).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NPIPB5	NM_001395849.1	c.854C>T	p.Pro285Leu	missense_variant	7/7	ENST00000424340.7	NP_001382778.1
LOC105371131	XR_007065022.1	n.150+3641G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NPIPB5	ENST00000424340.7	c.854C>T	p.Pro285Leu	missense_variant	7/7	1	NM_001395849.1	ENSP00000440703	P1

Frequencies

GnomAD3 genomes Cov.: 4

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000449 AC: 2 AN: 445892 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 237292

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000495

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000377

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 4

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 12, 2024

The c.854C>T (p.P285L) alteration is located in exon 7 (coding exon 7) of the NPIPB5 gene. This alteration results from a C to T substitution at nucleotide position 854, causing the proline (P) at amino acid position 285 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	Uncertain	0.36
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.095	.;.;T;T;.;.
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.81
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.77	.;T;T;.;T;.
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.33	T;T;T;T;T;T
MetaSVM	Benign	-0.96	T
MutationTaster	Benign	1.0	N;N
PROVEAN	Pathogenic	-4.9	D;.;D;D;D;.
REVEL	Benign	0.11
Sift	Uncertain	0.0010	D;.;D;D;D;.
Sift4G	Uncertain	0.0020	D;D;D;D;D;D
Polyphen		0.97	.;.;D;D;.;.
Vest4		0.084, 0.10, 0.10, 0.14
MutPred		0.54		Loss of catalytic residue at P285 (P = 0.0406);Loss of catalytic residue at P285 (P = 0.0406);Loss of catalytic residue at P285 (P = 0.0406);Loss of catalytic residue at P285 (P = 0.0406);Loss of catalytic residue at P285 (P = 0.0406);.;
MVP		0.36
ClinPred		0.97	D
Varity_R		0.071
gMVP		0.027

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: chr16-22545158;