16-22533903-G-A

Variant names:

• chr16-22533903-G-A
• NM_001395849.1:c.920G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001395849.1(NPIPB5):​c.920G>A​(p.Cys307Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict 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: 3)
  • Exomes 𝑓: 0.0000077 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NPIPB5 NM_001395849.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.83

Genes affected

NPIPB5 (HGNC:37233): (nuclear pore complex interacting protein family member B5) Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

LOC105371131 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.21231768).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPIPB5	NM_001395849.1	c.920G>A	p.Cys307Tyr	missense_variant	Exon 7 of 7	ENST00000424340.7	NP_001382778.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPIPB5	ENST00000424340.7	c.920G>A	p.Cys307Tyr	missense_variant	Exon 7 of 7	1	NM_001395849.1	ENSP00000440703.1

Frequencies

GnomAD3 genomes Cov.: 3

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000766 AC: 4 AN: 522098 Hom.: 0 Cov.: 5 AF XY: 0.00000352 AC XY: 1 AN XY: 284014

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000134

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 3

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 09, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.920G>A (p.C307Y) alteration is located in exon 7 (coding exon 7) of the NPIPB5 gene. This alteration results from a G to A substitution at nucleotide position 920, causing the cysteine (C) at amino acid position 307 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.60
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	14
DANN	Benign	0.48
DEOGEN2	Benign	0.11	.;.;T;T;.;.
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.073	N
LIST_S2	Benign	0.69	.;T;T;.;T;.
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.21	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
PROVEAN	Uncertain	-3.8	D;.;D;D;D;.
REVEL	Benign	0.057
Sift	Uncertain	0.012	D;.;D;D;D;.
Sift4G	Benign	0.24	T;D;D;D;T;T
Polyphen		0.56	.;.;P;P;.;.
Vest4		0.21, 0.17, 0.19, 0.19
MutPred		0.58		Gain of phosphorylation at C307 (P = 0.0297);Gain of phosphorylation at C307 (P = 0.0297);Gain of phosphorylation at C307 (P = 0.0297);Gain of phosphorylation at C307 (P = 0.0297);Gain of phosphorylation at C307 (P = 0.0297);.;
MVP		0.24
ClinPred		0.31	T
Varity_R		0.20
gMVP		0.013

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-22545224;