NM_001310137.5:c.1808C>G

Variant names:

• chr16-29383124-G-C
• rs536085707
• NM_001310137.5:c.1808C>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.1808C>G​(p.Pro603Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00272 in 1,569,374 control chromosomes in the GnomAD database, including 40 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0055 (4 hom., cov: 22)
  • Exomes 𝑓: 0.0024 (36 hom.)
• Consequence: NPIPB11 NM_001310137.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.123
• 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=0.004241675).
• BP6: Variant 16-29383124-G-C is Benign according to our data. Variant chr16-29383124-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 2646360.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPIPB11	NM_001310137.5	c.1808C>G	p.Pro603Arg	missense_variant	Exon 8 of 8	ENST00000698511.1	NP_001297066.2
NPIPB11	XM_047434576.1	c.1808C>G	p.Pro603Arg	missense_variant	Exon 7 of 8		XP_047290532.1
NPIPB11	XM_047434577.1	c.1442C>G	p.Pro481Arg	missense_variant	Exon 8 of 9		XP_047290533.1
NPIPB11	XM_047434578.1	c.1385C>G	p.Pro462Arg	missense_variant	Exon 8 of 9		XP_047290534.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPIPB11	ENST00000698511.1	c.1808C>G	p.Pro603Arg	missense_variant	Exon 8 of 8		NM_001310137.5	ENSP00000513761.1
NPIPB11	ENST00000524087.5	c.1808C>G	p.Pro603Arg	missense_variant	Exon 8 of 8	5		ENSP00000430853.1
RRN3P2	ENST00000769491.1	n.899+18065G>C		intron_variant	Intron 5 of 5

Frequencies

GnomAD3 genomes AF: 0.00554 AC: 760 AN: 137220 Hom.: 4 Cov.: 22

Gnomad AFR AF: 0.00195

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00579

Gnomad ASJ AF: 0.000614

Gnomad EAS AF: 0.000222

Gnomad SAS AF: 0.000722

Gnomad FIN AF: 0.00425

Gnomad MID AF: 0.00847

Gnomad NFE AF: 0.00866

Gnomad OTH AF: 0.00890

GnomAD2 exomes AF: 0.00208 AC: 508 AN: 244338 AF XY: 0.00186

Gnomad AFR exome AF: 0.000903

Gnomad AMR exome AF: 0.00205

Gnomad ASJ exome AF: 0.000201

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00236

Gnomad NFE exome AF: 0.00314

Gnomad OTH exome AF: 0.00335

GnomAD4 exome AF: 0.00245 AC: 3507 AN: 1432048 Hom.: 36 Cov.: 33 AF XY: 0.00254 AC XY: 1814 AN XY: 712920

African (AFR) AF: 0.000652 AC: 21 AN: 32216

American (AMR) AF: 0.00227 AC: 98 AN: 43188

Ashkenazi Jewish (ASJ) AF: 0.000310 AC: 8 AN: 25766

East Asian (EAS) AF: 0.00 AC: 0 AN: 38936

South Asian (SAS) AF: 0.000305 AC: 26 AN: 85142

European-Finnish (FIN) AF: 0.00351 AC: 185 AN: 52724

Middle Eastern (MID) AF: 0.000979 AC: 4 AN: 4086

European-Non Finnish (NFE) AF: 0.00273 AC: 2974 AN: 1091114

Other (OTH) AF: 0.00324 AC: 191 AN: 58876

GnomAD4 genome AF: 0.00553 AC: 760 AN: 137326 Hom.: 4 Cov.: 22 AF XY: 0.00529 AC XY: 355 AN XY: 67112

African (AFR) AF: 0.00195 AC: 71 AN: 36502

American (AMR) AF: 0.00579 AC: 81 AN: 14000

Ashkenazi Jewish (ASJ) AF: 0.000614 AC: 2 AN: 3258

East Asian (EAS) AF: 0.000222 AC: 1 AN: 4504

South Asian (SAS) AF: 0.000722 AC: 3 AN: 4156

European-Finnish (FIN) AF: 0.00425 AC: 39 AN: 9178

Middle Eastern (MID) AF: 0.00901 AC: 2 AN: 222

European-Non Finnish (NFE) AF: 0.00866 AC: 544 AN: 62796

Other (OTH) AF: 0.00885 AC: 17 AN: 1920

Alfa AF: 0.00207 Hom.: 0

ExAC AF: 0.00479 AC: 577

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 01, 2023

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	Uncertain	0.55
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0084	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0031	N
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.0042	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.34	N
PhyloP100		0.12
PROVEAN	Benign	-0.73	N
REVEL	Benign	0.017
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.0020	D
Vest4		0.13
MutPred		0.27		Gain of MoRF binding (P = 0.0087);
MVP		0.17
ClinPred		0.0042	T
Varity_R		0.087
gMVP		0.0057
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: rs536085707; hg19: chr16-29394445;