rs1555178358

Positions:

• chr12-68721868-G-A

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2 PP3_Strong PP5

The NM_020401.4(NUP107):​c.1339G>A​(p.Asp447Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: NUP107 NM_020401.4 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 9.36

Genes affected

NUP107 (HGNC:29914): (nucleoporin 107) This gene encodes a member of the nucleoporin family. The protein is localized to the nuclear rim and is an essential component of the nuclear pore complex (NPC). All molecules entering or leaving the nucleus either diffuse through or are actively transported by the NPC. Alternate transcriptional splice variants of this gene have been observed but have not been thoroughly characterized. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.94
• PP5: Variant 12-68721868-G-A is Pathogenic according to our data. Variant chr12-68721868-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 559482.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NUP107	NM_020401.4	c.1339G>A	p.Asp447Asn	missense_variant	16/28	ENST00000229179.9	NP_065134.1
NUP107	NM_001330192.2	c.1252G>A	p.Asp418Asn	missense_variant	16/28		NP_001317121.1
NUP107	XM_005269037.5	c.1279G>A	p.Asp427Asn	missense_variant	15/27		XP_005269094.1
NUP107	XM_047429177.1	c.403G>A	p.Asp135Asn	missense_variant	6/18		XP_047285133.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NUP107	ENST00000229179.9	c.1339G>A	p.Asp447Asn	missense_variant	16/28	1	NM_020401.4	ENSP00000229179.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Ovarian dysgenesis 6 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jul 23, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.75
BayesDel_addAF	Uncertain	0.077	D
BayesDel_noAF	Benign	-0.13
CADD	Pathogenic	33
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.68	D;.;.
Eigen	Pathogenic	0.85
Eigen_PC	Pathogenic	0.80
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.97	D;D;D
M_CAP	Uncertain	0.086	D
MetaRNN	Pathogenic	0.94	D;D;D
MetaSVM	Uncertain	0.18	D
MutationAssessor	Pathogenic	3.0	M;.;.
PrimateAI	Pathogenic	0.81	D
PROVEAN	Pathogenic	-4.8	D;D;D
REVEL	Uncertain	0.60
Sift	Pathogenic	0.0	D;D;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		1.0	D;.;.
Vest4		0.99
MutPred		0.77		Loss of phosphorylation at T444 (P = 0.1375);.;.;
MVP		0.75
MPC		0.89
ClinPred		1.0	D
GERP RS		5.0
Varity_R		0.89
gMVP		0.81

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.18		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1555178358; hg19: chr12-69115648;