chr16-29383273-C-G

Variant names:

• chr16-29383273-C-G
• rs78268573
• NM_001310137.5:c.1659G>C

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001310137.5(NPIPB11):​c.1659G>C​(p.Ala553Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.012 (14 hom., cov: 20)
  • Exomes 𝑓: 0.0040 (286 hom.)
  • Failed GnomAD Quality Control
• Consequence: NPIPB11 NM_001310137.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.32
• 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: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 16-29383273-C-G is Benign according to our data. Variant chr16-29383273-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2672626.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.32 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 14 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPIPB11	NM_001310137.5	c.1659G>C	p.Ala553Ala	synonymous_variant	Exon 8 of 8	ENST00000698511.1	NP_001297066.2
NPIPB11	XM_047434576.1	c.1659G>C	p.Ala553Ala	synonymous_variant	Exon 7 of 8		XP_047290532.1
NPIPB11	XM_047434577.1	c.1293G>C	p.Ala431Ala	synonymous_variant	Exon 8 of 9		XP_047290533.1
NPIPB11	XM_047434578.1	c.1236G>C	p.Ala412Ala	synonymous_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.1659G>C	p.Ala553Ala	synonymous_variant	Exon 8 of 8		NM_001310137.5	ENSP00000513761.1
NPIPB11	ENST00000524087.5	c.1659G>C	p.Ala553Ala	synonymous_variant	Exon 8 of 8	5		ENSP00000430853.1
RRN3P2	ENST00000769491.1	n.899+18214C>G		intron_variant	Intron 5 of 5

Frequencies

GnomAD3 genomes AF: 0.0122 AC: 1454 AN: 119062 Hom.: 14 Cov.: 20

Gnomad AFR AF: 0.00355

Gnomad AMI AF: 0.00581

Gnomad AMR AF: 0.0109

Gnomad ASJ AF: 0.0277

Gnomad EAS AF: 0.000932

Gnomad SAS AF: 0.00392

Gnomad FIN AF: 0.0146

Gnomad MID AF: 0.00505

Gnomad NFE AF: 0.0183

Gnomad OTH AF: 0.0106

GnomAD2 exomes AF: 0.00407 AC: 907 AN: 222842 AF XY: 0.00393

Gnomad AFR exome AF: 0.00195

Gnomad AMR exome AF: 0.00383

Gnomad ASJ exome AF: 0.00435

Gnomad EAS exome AF: 0.000225

Gnomad FIN exome AF: 0.00714

Gnomad NFE exome AF: 0.00531

Gnomad OTH exome AF: 0.00384

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00395 AC: 5474 AN: 1385182 Hom.: 286 Cov.: 49 AF XY: 0.00411 AC XY: 2826 AN XY: 688004

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

African (AFR) AF: 0.00168 AC: 54 AN: 32206

American (AMR) AF: 0.00325 AC: 139 AN: 42734

Ashkenazi Jewish (ASJ) AF: 0.0112 AC: 260 AN: 23126

East Asian (EAS) AF: 0.0000255 AC: 1 AN: 39288

South Asian (SAS) AF: 0.00176 AC: 142 AN: 80864

European-Finnish (FIN) AF: 0.0163 AC: 709 AN: 43522

Middle Eastern (MID) AF: 0.0114 AC: 43 AN: 3756

European-Non Finnish (NFE) AF: 0.00357 AC: 3801 AN: 1063412

Other (OTH) AF: 0.00578 AC: 325 AN: 56274

⚠️ 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: 0.0122 AC: 1454 AN: 119156 Hom.: 14 Cov.: 20 AF XY: 0.0116 AC XY: 672 AN XY: 57882

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

African (AFR) AF: 0.00354 AC: 116 AN: 32758

American (AMR) AF: 0.0108 AC: 131 AN: 12078

Ashkenazi Jewish (ASJ) AF: 0.0277 AC: 75 AN: 2706

East Asian (EAS) AF: 0.000934 AC: 4 AN: 4282

South Asian (SAS) AF: 0.00393 AC: 15 AN: 3814

European-Finnish (FIN) AF: 0.0146 AC: 106 AN: 7256

Middle Eastern (MID) AF: 0.00538 AC: 1 AN: 186

European-Non Finnish (NFE) AF: 0.0183 AC: 985 AN: 53778

Other (OTH) AF: 0.0106 AC: 17 AN: 1610

⚠️ 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: 0.0139 Hom.: 2

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 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
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.9
DANN	Benign	0.49
PhyloP100		-1.3
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: rs78268573; hg19: chr16-29394594;