16-22533848-G-C

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_001395849.1(NPIPB5):c.865G>C(p.Val289Leu) 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 Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.013 (0 hom., cov: 0)
  • Exomes 𝑓: 0.077 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NPIPB5 NM_001395849.1 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.86

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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0019716918).
• BP6: Variant 16-22533848-G-C is Benign according to our data. Variant chr16-22533848-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 2342066.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NPIPB5	NM_001395849.1	c.865G>C	p.Val289Leu	missense_variant	7/7	ENST00000424340.7
LOC105371131	XR_007065022.1	n.150+3630C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPIPB5	ENST00000424340.7	c.865G>C	p.Val289Leu	missense_variant	7/7	1	NM_001395849.1	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 39 AN: 2938 Hom.: 0 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.00943

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0138

Gnomad ASJ AF: 0.0256

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0526

Gnomad FIN AF: 0.0282

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0140

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.415 AC: 568 AN: 1368 Hom.: 0 AF XY: 0.406 AC XY: 286 AN XY: 704

Gnomad AFR exome AF: 0.309

Gnomad AMR exome AF: 0.439

Gnomad ASJ exome AF: 0.423

Gnomad EAS exome AF: 0.426

Gnomad SAS exome AF: 0.443

Gnomad FIN exome AF: 0.500

Gnomad NFE exome AF: 0.406

Gnomad OTH exome AF: 0.432

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0770 AC: 11913 AN: 154812 Hom.: 0 Cov.: 0 AF XY: 0.0719 AC XY: 6081 AN XY: 84632

Gnomad4 AFR exome AF: 0.0780

Gnomad4 AMR exome AF: 0.122

Gnomad4 ASJ exome AF: 0.0936

Gnomad4 EAS exome AF: 0.0728

Gnomad4 SAS exome AF: 0.0856

Gnomad4 FIN exome AF: 0.0291

Gnomad4 NFE exome AF: 0.0775

Gnomad4 OTH exome AF: 0.0856

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0132 AC: 39 AN: 2962 Hom.: 0 Cov.: 0 AF XY: 0.0145 AC XY: 22 AN XY: 1514

Gnomad4 AFR AF: 0.00924

Gnomad4 AMR AF: 0.0137

Gnomad4 ASJ AF: 0.0256

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0526

Gnomad4 FIN AF: 0.0282

Gnomad4 NFE AF: 0.0140

Gnomad4 OTH AF: 0.00

Alfa AF: 0.175 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 13, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
Cadd	Benign	0.15
Dann	Benign	0.23
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.021	N
M_CAP	Benign	0.0018	T
MetaRNN	Benign	0.0020	T;T;T;T;T;T
MetaSVM	Benign	-0.94	T
MutationTaster	Benign	1.0	N;N
PROVEAN	Benign	0.67	N;.;N;N;N;N
REVEL	Benign	0.017
Sift	Benign	0.77	T;.;T;T;T;T
Sift4G	Benign	0.74	T;T;T;T;T;T
Polyphen		0.0010	.;.;B;B;.;.
Vest4		0.071, 0.075, 0.069, 0.058
MutPred		0.37		Gain of catalytic residue at V289 (P = 0.0218);Gain of catalytic residue at V289 (P = 0.0218);Gain of catalytic residue at V289 (P = 0.0218);Gain of catalytic residue at V289 (P = 0.0218);Gain of catalytic residue at V289 (P = 0.0218);.;
ClinPred		0.0015	T
Varity_R		0.097
gMVP		0.0049

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: rs28448386; hg19: chr16-22545169;