16-29383501-A-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_001310137.5(NPIPB11):​c.1431T>C​(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. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00038 (0 hom., cov: 9)
  • Exomes 𝑓: 0.0012 (232 hom.)
  • Failed GnomAD Quality Control
• Consequence: NPIPB11 NM_001310137.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.07).
• BP6: Variant 16-29383501-A-G is Benign according to our data. Variant chr16-29383501-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2646361.Status of the report is criteria_provided_single_submitter, 1 stars.
• 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>C	p.Ser477Ser	synonymous_variant	Exon 8 of 8	ENST00000698511.1	NP_001297066.2
NPIPB11	XM_047434576.1	c.1431T>C	p.Ser477Ser	synonymous_variant	Exon 7 of 8		XP_047290532.1
NPIPB11	XM_047434577.1	c.1086-21T>C		intron_variant	Intron 7 of 8		XP_047290533.1
NPIPB11	XM_047434578.1	c.1029-21T>C		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>C	p.Ser477Ser	synonymous_variant	Exon 8 of 8		NM_001310137.5	ENSP00000513761.1
NPIPB11	ENST00000524087.5	c.1431T>C	p.Ser477Ser	synonymous_variant	Exon 8 of 8	5		ENSP00000430853.1
RRN3P2	ENST00000769491.1	n.899+18442A>G		intron_variant	Intron 5 of 5

Frequencies

GnomAD3 genomes AF: 0.000384 AC: 25 AN: 65060 Hom.: 0 Cov.: 9

Gnomad AFR AF: 0.000119

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000179

Gnomad ASJ AF: 0.000566

Gnomad EAS AF: 0.00364

Gnomad SAS AF: 0.000906

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000494

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00235 AC: 453 AN: 192582 AF XY: 0.00220

Gnomad AFR exome AF: 0.000998

Gnomad AMR exome AF: 0.00348

Gnomad ASJ exome AF: 0.00440

Gnomad EAS exome AF: 0.00229

Gnomad FIN exome AF: 0.00130

Gnomad NFE exome AF: 0.00226

Gnomad OTH exome AF: 0.00580

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00117 AC: 1389 AN: 1186790 Hom.: 232 Cov.: 34 AF XY: 0.00127 AC XY: 753 AN XY: 592172

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

African (AFR) AF: 0.000391 AC: 12 AN: 30670

American (AMR) AF: 0.00167 AC: 58 AN: 34630

Ashkenazi Jewish (ASJ) AF: 0.00344 AC: 67 AN: 19452

East Asian (EAS) AF: 0.000677 AC: 17 AN: 25102

South Asian (SAS) AF: 0.00250 AC: 187 AN: 74664

European-Finnish (FIN) AF: 0.00316 AC: 106 AN: 33584

Middle Eastern (MID) AF: 0.00216 AC: 7 AN: 3240

European-Non Finnish (NFE) AF: 0.000941 AC: 862 AN: 916424

Other (OTH) AF: 0.00149 AC: 73 AN: 49024

⚠️ 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: 0.000384 AC: 25 AN: 65098 Hom.: 0 Cov.: 9 AF XY: 0.000425 AC XY: 13 AN XY: 30590

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

African (AFR) AF: 0.000118 AC: 2 AN: 16884

American (AMR) AF: 0.000179 AC: 1 AN: 5598

Ashkenazi Jewish (ASJ) AF: 0.000566 AC: 1 AN: 1768

East Asian (EAS) AF: 0.00365 AC: 3 AN: 822

South Asian (SAS) AF: 0.000916 AC: 1 AN: 1092

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3212

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 104

European-Non Finnish (NFE) AF: 0.000494 AC: 17 AN: 34410

Other (OTH) AF: 0.00 AC: 0 AN: 844

⚠️ 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: 0.00 Hom.: 0

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	-1.1
CADD	Benign	3.8
DANN	Benign	0.27
PhyloP100		-2.5
Mutation Taster		=100/0	polymorphism (auto)

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; COSMIC: COSV105936522; COSMIC: COSV105936522;