chr6-149736587-C-T

Variant names:

• chr6-149736587-C-T
• NM_198887.3:c.674G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_198887.3(NUP43):​c.674G>A​(p.Arg225Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: NUP43 NM_198887.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.58
• Publications: 0 publications found

Genes affected

NUP43 (HGNC:21182): (nucleoporin 43) Bidirectional transport of macromolecules between the cytoplasm and nucleus occurs through nuclear pore complexes (NPCs) embedded in the nuclear envelope. NPCs are composed of subcomplexes, and NUP43 is part of one such subcomplex, Nup107-160 (Loiodice et al., 2004 [PubMed 15146057]).[supplied by OMIM, Mar 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3307078).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198887.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUP43	NM_198887.3	MANE Select	c.674G>A	p.Arg225Lys	missense	Exon 6 of 8	NP_942590.1	Q8NFH3-1
	NUP43	NR_104456.2		n.708G>A		non_coding_transcript_exon	Exon 6 of 9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUP43	ENST00000340413.7	TSL:1 MANE Select	c.674G>A	p.Arg225Lys	missense	Exon 6 of 8	ENSP00000342262.2	Q8NFH3-1
	NUP43	ENST00000917625.1		c.674G>A	p.Arg225Lys	missense	Exon 6 of 9	ENSP00000587684.1
	NUP43	ENST00000917622.1		c.674G>A	p.Arg225Lys	missense	Exon 7 of 9	ENSP00000587681.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.042	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0085	T
Eigen	Benign	-0.017
Eigen_PC	Benign	0.22
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.74	N
PhyloP100		5.6
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-0.54	N
REVEL	Benign	0.096
Sift	Benign	0.45	T
Sift4G	Benign	0.61	T
Polyphen		0.074	B
Vest4		0.48
MutPred		0.67		Gain of ubiquitination at R225 (P = 0.0337)
MVP		0.65
MPC		0.15
ClinPred		0.43	T
GERP RS		5.7
Varity_R		0.29
gMVP		0.62
Mutation Taster		=65/35	polymorphism

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

hg19: chr6-150057723;