16-22534157-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001395849.1(NPIPB5):c.1174C>G(p.Gln392Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q392L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 5)
• Consequence: NPIPB5 NM_001395849.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.00100

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 -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.09940684).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NPIPB5	NM_001395849.1	c.1174C>G	p.Gln392Glu	missense_variant	7/7	ENST00000424340.7
LOC105371131	XR_007065022.1	n.150+3321G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPIPB5	ENST00000424340.7	c.1174C>G	p.Gln392Glu	missense_variant	7/7	1	NM_001395849.1	P1

Frequencies

GnomAD3 genomes Cov.: 5

GnomAD4 exome Cov.: 4

GnomAD4 genome Cov.: 5

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

Apr 12, 2022

The c.1174C>G (p.Q392E) alteration is located in exon 7 (coding exon 7) of the NPIPB5 gene. This alteration results from a C to G substitution at nucleotide position 1174, causing the glutamine (Q) at amino acid position 392 to be replaced by a glutamic acid (E). 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	0.20
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
Cadd	Benign	4.8
Dann	Benign	0.75
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.023	N
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.099	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N;N
PROVEAN	Benign	-0.27	N;.;N;N;N;.
REVEL	Benign	0.087
Sift	Benign	1.0	T;.;T;T;T;.
Sift4G	Benign	1.0	T;T;T;T;T;T
Polyphen		0.90	.;.;P;P;.;.
Vest4		0.041, 0.058, 0.080, 0.065
MutPred		0.10		Gain of glycosylation at T387 (P = 0.1425);Gain of glycosylation at T387 (P = 0.1425);Gain of glycosylation at T387 (P = 0.1425);Gain of glycosylation at T387 (P = 0.1425);Gain of glycosylation at T387 (P = 0.1425);.;
MVP		0.014
ClinPred		0.11	T
Varity_R		0.16
gMVP		0.0024

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: chr16-22545478;