16-22533974-C-A

Variant names:

• chr16-22533974-C-A
• NM_001395849.1:c.991C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001395849.1(NPIPB5):​c.991C>A​(p.Leu331Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/17 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: 13)
• Consequence: NPIPB5 NM_001395849.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.908

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.122232586).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPIPB5	NM_001395849.1	c.991C>A	p.Leu331Ile	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.991C>A	p.Leu331Ile	missense_variant	Exon 7 of 7	1	NM_001395849.1	ENSP00000440703.1

Frequencies

GnomAD3 genomes Cov.: 13

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 13

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.043	.;.;T;T;.;.
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.66
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.80	.;T;T;.;T;.
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.12	T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
PROVEAN	Benign	-0.76	N;.;N;N;N;.
REVEL	Benign	0.035
Sift	Benign	0.055	T;.;D;D;T;.
Sift4G	Benign	0.43	T;T;T;T;T;T
Polyphen		0.58	.;.;P;P;.;.
Vest4		0.18, 0.12, 0.18, 0.16
MutPred		0.32		Gain of catalytic residue at P333 (P = 0.0546);Gain of catalytic residue at P333 (P = 0.0546);Gain of catalytic residue at P333 (P = 0.0546);Gain of catalytic residue at P333 (P = 0.0546);Gain of catalytic residue at P333 (P = 0.0546);.;
MVP		0.030
ClinPred		0.32	T
Varity_R		0.16
gMVP		0.0031

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: chr16-22545295;