16-22533858-C-A

Variant names:

• chr16-22533858-C-A
• NM_001395849.1:c.875C>A

Variant summary

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

The NM_001395849.1(NPIPB5):​c.875C>A​(p.Pro292His) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 11/17 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: 0.000020 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NPIPB5 NM_001395849.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.908

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=0.28020945).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPIPB5	NM_001395849.1	c.875C>A	p.Pro292His	missense_variant	Exon 7 of 7	ENST00000424340.7	NP_001382778.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPIPB5	ENST00000424340.7	c.875C>A	p.Pro292His	missense_variant	Exon 7 of 7	1	NM_001395849.1	ENSP00000440703.1

Frequencies

GnomAD3 genomes Cov.: 4

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000205 AC: 9 AN: 439914 Hom.: 0 Cov.: 0 AF XY: 0.0000171 AC XY: 4 AN XY: 234226

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000519

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: 0.0000305

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

Nov 08, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.875C>A (p.P292H) alteration is located in exon 7 (coding exon 7) of the NPIPB5 gene. This alteration results from a C to A substitution at nucleotide position 875, causing the proline (P) at amino acid position 292 to be replaced by a histidine (H). 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	Pathogenic	0.66
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	18
DANN	Benign	0.97
DEOGEN2	Benign	0.13	.;.;T;T;.;.
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.042	N
LIST_S2	Benign	0.61	.;T;T;.;T;.
M_CAP	Benign	0.0038	T
MetaRNN	Benign	0.28	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
PROVEAN	Pathogenic	-4.8	D;.;D;D;D;.
REVEL	Benign	0.14
Sift	Pathogenic	0.0	D;.;D;D;D;.
Sift4G	Uncertain	0.049	D;T;D;D;D;D
Polyphen		1.0	.;.;D;D;.;.
Vest4		0.31, 0.33, 0.33, 0.41
MutPred		0.47		Loss of glycosylation at P292 (P = 0.0607);Loss of glycosylation at P292 (P = 0.0607);Loss of glycosylation at P292 (P = 0.0607);Loss of glycosylation at P292 (P = 0.0607);Loss of glycosylation at P292 (P = 0.0607);.;
MVP		0.21
ClinPred		0.95	D
Varity_R		0.21
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: chr16-22545179;