16-29384067-G-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001310137.5(NPIPB11):​c.865C>T​(p.Leu289Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000898 in 1,113,690 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 11)
  • Exomes 𝑓: 9.0e-7 (0 hom.)
• Consequence: NPIPB11 NM_001310137.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.289
• Publications: 0 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP7: Synonymous conserved (PhyloP=0.289 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPIPB11	NM_001310137.5	c.865C>T	p.Leu289Leu	synonymous_variant	Exon 8 of 8	ENST00000698511.1	NP_001297066.2
NPIPB11	XM_047434576.1	c.865C>T	p.Leu289Leu	synonymous_variant	Exon 7 of 8		XP_047290532.1
NPIPB11	XM_047434577.1	c.865C>T	p.Leu289Leu	synonymous_variant	Exon 7 of 9		XP_047290533.1
NPIPB11	XM_047434578.1	c.808C>T	p.Leu270Leu	synonymous_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>T	p.Leu289Leu	synonymous_variant	Exon 8 of 8		NM_001310137.5	ENSP00000513761.1
NPIPB11	ENST00000524087.5	c.865C>T	p.Leu289Leu	synonymous_variant	Exon 8 of 8	5		ENSP00000430853.1
RRN3P2	ENST00000769491.1	n.899+19008G>A		intron_variant	Intron 5 of 5

Frequencies

GnomAD3 genomes Cov.: 11

GnomAD4 exome AF: 8.98e-7 AC: 1 AN: 1113690 Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0 AN XY: 562880

African (AFR) AF: 0.00 AC: 0 AN: 20318

American (AMR) AF: 0.00 AC: 0 AN: 36894

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20462

East Asian (EAS) AF: 0.00 AC: 0 AN: 34716

South Asian (SAS) AF: 0.00 AC: 0 AN: 72034

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35880

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3100

European-Non Finnish (NFE) AF: 0.00000119 AC: 1 AN: 843116

Other (OTH) AF: 0.00 AC: 0 AN: 47170

GnomAD4 genome Cov.: 11

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.5
DANN	Benign	0.68
PhyloP100		0.29

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;