16-29384067-G-C

Variant names:

• chr16-29384067-G-C
• rs202027988
• NM_001310137.5:c.865C>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001310137.5(NPIPB11):​c.865C>G​(p.Leu289Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00255 in 1,194,374 control chromosomes in the GnomAD database, including 162 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0030 (3 hom., cov: 11)
  • Exomes 𝑓: 0.0025 (159 hom.)
• Consequence: NPIPB11 NM_001310137.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.289
• Publications: 3 publications found

Genes affected

NPIPB11 (HGNC:37453): (nuclear pore complex interacting protein family member B11) Predicted to act upstream of or within prevention of polyspermy. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

RRN3P2 (HGNC:37619): (RRN3 pseudogene 2) Predicted to enable RNA polymerase I core binding activity and RNA polymerase I general transcription initiation factor activity. Predicted to be involved in transcription initiation from RNA polymerase I promoter. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.020652711).
• BP6: Variant 16-29384067-G-C is Benign according to our data. Variant chr16-29384067-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 3770523.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPIPB11	NM_001310137.5	c.865C>G	p.Leu289Val	missense_variant	Exon 8 of 8	ENST00000698511.1	NP_001297066.2
NPIPB11	XM_047434576.1	c.865C>G	p.Leu289Val	missense_variant	Exon 7 of 8		XP_047290532.1
NPIPB11	XM_047434577.1	c.865C>G	p.Leu289Val	missense_variant	Exon 7 of 9		XP_047290533.1
NPIPB11	XM_047434578.1	c.808C>G	p.Leu270Val	missense_variant	Exon 7 of 9		XP_047290534.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPIPB11	ENST00000698511.1	c.865C>G	p.Leu289Val	missense_variant	Exon 8 of 8		NM_001310137.5	ENSP00000513761.1
NPIPB11	ENST00000524087.5	c.865C>G	p.Leu289Val	missense_variant	Exon 8 of 8	5		ENSP00000430853.1
RRN3P2	ENST00000769491.1	n.899+19008G>C		intron_variant	Intron 5 of 5

Frequencies

GnomAD3 genomes AF: 0.00302 AC: 269 AN: 89206 Hom.: 3 Cov.: 11

Gnomad AFR AF: 0.000514

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00293

Gnomad ASJ AF: 0.00737

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000473

Gnomad FIN AF: 0.00168

Gnomad MID AF: 0.00658

Gnomad NFE AF: 0.00426

Gnomad OTH AF: 0.000864

GnomAD2 exomes AF: 0.000760 AC: 74 AN: 97422 AF XY: 0.000698

Gnomad AFR exome AF: 0.000791

Gnomad AMR exome AF: 0.000896

Gnomad ASJ exome AF: 0.00128

Gnomad EAS exome AF: 0.000542

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000897

Gnomad OTH exome AF: 0.00138

GnomAD4 exome AF: 0.00252 AC: 2780 AN: 1105078 Hom.: 159 Cov.: 27 AF XY: 0.00250 AC XY: 1395 AN XY: 558558

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00133 AC: 27 AN: 20300

American (AMR) AF: 0.00336 AC: 123 AN: 36634

Ashkenazi Jewish (ASJ) AF: 0.00915 AC: 183 AN: 19994

East Asian (EAS) AF: 0.000749 AC: 26 AN: 34704

South Asian (SAS) AF: 0.00173 AC: 124 AN: 71850

European-Finnish (FIN) AF: 0.00402 AC: 143 AN: 35534

Middle Eastern (MID) AF: 0.00589 AC: 18 AN: 3056

European-Non Finnish (NFE) AF: 0.00236 AC: 1971 AN: 836324

Other (OTH) AF: 0.00353 AC: 165 AN: 46682

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00301 AC: 269 AN: 89296 Hom.: 3 Cov.: 11 AF XY: 0.00283 AC XY: 121 AN XY: 42722

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000512 AC: 9 AN: 17578

American (AMR) AF: 0.00293 AC: 26 AN: 8886

Ashkenazi Jewish (ASJ) AF: 0.00737 AC: 16 AN: 2172

East Asian (EAS) AF: 0.00 AC: 0 AN: 2104

South Asian (SAS) AF: 0.000474 AC: 1 AN: 2110

European-Finnish (FIN) AF: 0.00168 AC: 11 AN: 6566

Middle Eastern (MID) AF: 0.00694 AC: 1 AN: 144

European-Non Finnish (NFE) AF: 0.00426 AC: 204 AN: 47902

Other (OTH) AF: 0.000846 AC: 1 AN: 1182

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0183 Hom.: 3

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Feb 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

NPIPB11: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	9.2
DANN	Benign	0.45
DEOGEN2	Benign	0.0050	T
Eigen	Benign	-0.90
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0030	N
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.021	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.2	L
PhyloP100		0.29
PROVEAN	Benign	-0.14	N
REVEL	Benign	0.057
Sift	Benign	0.81	T
Sift4G	Benign	0.68	T
Vest4		0.13
MutPred		0.60		Loss of catalytic residue at L289 (P = 0.0231);
MVP		0.067
ClinPred		0.0042	T
Varity_R		0.064
gMVP		0.012
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs202027988; hg19: chr16-29395388; COSMIC: COSV67325493; COSMIC: COSV67325493;