chr16-56748383-C-A

Variant names:

• chr16-56748383-C-A
• NM_014669.5:c.136C>A

Variant summary

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

The NM_014669.5(NUP93):​c.136C>A​(p.Arg46Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NUP93 NM_014669.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.74

Genes affected

NUP93 (HGNC:28958): (nucleoporin 93) The nuclear pore complex is a massive structure that extends across the nuclear envelope, forming a gateway that regulates the flow of macromolecules between the nucleus and the cytoplasm. Nucleoporins are the main components of the nuclear pore complex in eukaryotic cells. This gene encodes a nucleoporin protein that localizes both to the basket of the pore and to the nuclear entry of the central gated channel of the pore. The encoded protein is a target of caspase cysteine proteases that play a central role in programmed cell death by apoptosis. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUP93	NM_014669.5	c.136C>A	p.Arg46Ser	missense_variant	Exon 2 of 22	ENST00000308159.10	NP_055484.3
NUP93	XM_005256263.4	c.136C>A	p.Arg46Ser	missense_variant	Exon 2 of 22		XP_005256320.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUP93	ENST00000308159.10	c.136C>A	p.Arg46Ser	missense_variant	Exon 2 of 22	1	NM_014669.5	ENSP00000310668.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.79
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.25	T;T;T;T;T
Eigen	Uncertain	0.23
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.95	D;D;D;D;D
M_CAP	Benign	0.026	D
MetaRNN	Uncertain	0.51	D;D;D;D;D
MetaSVM	Benign	-0.91	T
MutationAssessor	Uncertain	2.0	M;.;.;.;.
PrimateAI	Pathogenic	0.85	D
PROVEAN	Uncertain	-4.2	D;D;D;D;D
REVEL	Benign	0.25
Sift	Uncertain	0.0030	D;D;D;D;D
Sift4G	Uncertain	0.016	D;D;D;D;D
Polyphen		0.024	B;.;.;.;.
Vest4		0.80
MutPred		0.48		Loss of MoRF binding (P = 0.012);Loss of MoRF binding (P = 0.012);Loss of MoRF binding (P = 0.012);Loss of MoRF binding (P = 0.012);Loss of MoRF binding (P = 0.012);
MVP		0.70
MPC		0.80
ClinPred		0.98	D
GERP RS		6.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7
Varity_R		0.76
gMVP		0.79

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr16-56782295;