chr16-29383501-A-T

Variant names:

• chr16-29383501-A-T
• rs376240593
• NM_001310137.5:c.1431T>A

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BP7

The NM_001310137.5(NPIPB11):​c.1431T>A​(p.Ser477Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S477S) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 9)
  • Exomes 𝑓: 0.0000025 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NPIPB11 NM_001310137.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.47
• 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 -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.09).
• BP7: Synonymous conserved (PhyloP=-2.47 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPIPB11	NM_001310137.5	c.1431T>A	p.Ser477Ser	synonymous_variant	Exon 8 of 8	ENST00000698511.1	NP_001297066.2
NPIPB11	XM_047434576.1	c.1431T>A	p.Ser477Ser	synonymous_variant	Exon 7 of 8		XP_047290532.1
NPIPB11	XM_047434577.1	c.1086-21T>A		intron_variant	Intron 7 of 8		XP_047290533.1
NPIPB11	XM_047434578.1	c.1029-21T>A		intron_variant	Intron 7 of 8		XP_047290534.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPIPB11	ENST00000698511.1	c.1431T>A	p.Ser477Ser	synonymous_variant	Exon 8 of 8		NM_001310137.5	ENSP00000513761.1
NPIPB11	ENST00000524087.5	c.1431T>A	p.Ser477Ser	synonymous_variant	Exon 8 of 8	5		ENSP00000430853.1
RRN3P2	ENST00000769491.1	n.899+18442A>T		intron_variant	Intron 5 of 5

Frequencies

GnomAD3 genomes Cov.: 9

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000252 AC: 3 AN: 1190528 Hom.: 0 Cov.: 34 AF XY: 0.00000168 AC XY: 1 AN XY: 594118

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

African (AFR) AF: 0.00 AC: 0 AN: 30698

American (AMR) AF: 0.0000288 AC: 1 AN: 34760

Ashkenazi Jewish (ASJ) AF: 0.0000510 AC: 1 AN: 19596

East Asian (EAS) AF: 0.00 AC: 0 AN: 25144

South Asian (SAS) AF: 0.00 AC: 0 AN: 75148

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33778

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3256

European-Non Finnish (NFE) AF: 0.00000109 AC: 1 AN: 918936

Other (OTH) AF: 0.00 AC: 0 AN: 49212

⚠️ 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 Cov.: 9

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	3.3
DANN	Benign	0.29
PhyloP100		-2.5

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: rs376240593; hg19: chr16-29394822;