16-22534103-C-T

Position:

• chr16-22534103-C-T

Variant summary

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

The NM_001395849.1(NPIPB5):​c.1120C>T​(p.Leu374Phe) 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: 9)
  • Exomes 𝑓: 0.0000011 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NPIPB5 NM_001395849.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.67

Genes affected

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

NPIPB5 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.1252526).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NPIPB5	NM_001395849.1	c.1120C>T	p.Leu374Phe	missense_variant	7/7	ENST00000424340.7	NP_001382778.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NPIPB5	ENST00000424340.7	c.1120C>T	p.Leu374Phe	missense_variant	7/7	1	NM_001395849.1	ENSP00000440703.1

Frequencies

GnomAD3 genomes Cov.: 9

GnomAD3 exomes AF: 0.0000167 AC: 1 AN: 60054 Hom.: 0 AF XY: 0.0000326 AC XY: 1 AN XY: 30642

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000488

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000110 AC: 1 AN: 905088 Hom.: 0 Cov.: 14 AF XY: 0.00000213 AC XY: 1 AN XY: 468822

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000277

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 9

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

Dec 14, 2023

The c.1120C>T (p.L374F) 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 1120, causing the leucine (L) at amino acid position 374 to be replaced by a phenylalanine (F). 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	0.37
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	13
DANN	Uncertain	0.99
DEOGEN2	Benign	0.022	.;.;T;T;.;.
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.033	N
LIST_S2	Benign	0.52	.;T;T;.;T;.
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.13	T;T;T;T;T;T
MetaSVM	Benign	-0.99	T
PROVEAN	Benign	-1.2	N;.;N;N;N;.
REVEL	Benign	0.080
Sift	Benign	0.28	T;.;T;T;T;.
Sift4G	Benign	0.39	T;T;T;T;T;T
Polyphen		0.98	.;.;D;D;.;.
Vest4		0.11, 0.13, 0.13, 0.071
MutPred		0.24		Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);.;
MVP		0.048
ClinPred		0.10	T
Varity_R		0.088
gMVP		0.0020

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

LitVar

Other links and lift over

dbSNP: rs1567384929; hg19: chr16-22545424;