12-102074419-G-C

Variant names:

• chr12-102074419-G-C
• rs746341112
• NM_024057.4:c.916C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_024057.4(NUP37):​c.916C>G​(p.Arg306Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R306Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NUP37 NM_024057.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.91
• Publications: 0 publications found

Genes affected

NUP37 (HGNC:29929): (nucleoporin 37) Nuclear pore complexes (NPCs) are used for transporting macromolecules between the cytoplasm and the nucleus. NPCs consist of multiple copies of 30 distinct proteins (nucleoporins), which assemble into biochemically-separable subcomplexes. The protein encoded by this gene is part of a subcomplex (Nup107-160) that is required for proper NPC function as well as for normal kinetochore-microtubule interaction and mitosis. [provided by RefSeq, Dec 2015]

NUP37 Gene-Disease associations (from GenCC):

• familial idiopathic steroid-resistant nephrotic syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000257222 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 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
NUP37	NM_024057.4	c.916C>G	p.Arg306Gly	missense_variant	Exon 10 of 10	ENST00000552283.6	NP_076962.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUP37	ENST00000552283.6	c.916C>G	p.Arg306Gly	missense_variant	Exon 10 of 10	5	NM_024057.4	ENSP00000448054.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.074	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.074	T;T
Eigen	Benign	0.073
Eigen_PC	Benign	0.071
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.94	.;D
M_CAP	Benign	0.020	T
MetaRNN	Uncertain	0.64	D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.5	M;M
PhyloP100		2.9
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-1.8	N;N
REVEL	Benign	0.17
Sift	Benign	0.11	T;T
Sift4G	Benign	0.41	T;T
Polyphen		0.83	P;P
Vest4		0.64
MutPred		0.58		Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);
MVP		0.37
MPC		0.36
ClinPred		0.94	D
GERP RS		-0.50
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.23
gMVP		0.40
Mutation Taster		=72/28	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

dbSNP: rs746341112; hg19: chr12-102468197;