1-153992870-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2 PP2 BP4

The ENST00000368559.8(NUP210L):c.5632C>T(p.Arg1878Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,102 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: NUP210L ENST00000368559.8 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.172

Genes affected

NUP210L (HGNC:29915): (nucleoporin 210 like) Predicted to act upstream of or within Sertoli cell development and spermatid development. Predicted to be integral component of membrane. Predicted to be part of nuclear pore. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, NUP210L
• BP4: Computational evidence support a benign effect (MetaRNN=0.3401564).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NUP210L	NM_207308.3	c.5632C>T	p.Arg1878Trp	missense_variant	40/40	ENST00000368559.8
NUP210L	XM_011510122.2	c.5500C>T	p.Arg1834Trp	missense_variant	39/39

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NUP210L	ENST00000368559.8	c.5632C>T	p.Arg1878Trp	missense_variant	40/40	5	NM_207308.3	P2
NUP210L	ENST00000368553.5	c.1975C>T	p.Arg659Trp	missense_variant	16/16	1		A2
NUP210L	ENST00000271854.3	c.5176C>T	p.Arg1726Trp	missense_variant	38/38	5		A2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.00000804 AC: 2 AN: 248748 Hom.: 0 AF XY: 0.00000741 AC XY: 1 AN XY: 134988

Gnomad AFR exome AF: 0.0000647

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000884

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461102 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726880

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

Alfa AF: 0.0000312 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 20, 2023

The c.5632C>T (p.R1878W) alteration is located in exon 40 (coding exon 40) of the NUP210L gene. This alteration results from a C to T substitution at nucleotide position 5632, causing the arginine (R) at amino acid position 1878 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.34
Cadd	Benign	21
Dann	Uncertain	1.0
DEOGEN2	Benign	0.38	T;T;.
Eigen	Benign	0.071
Eigen_PC	Benign	-0.041
FATHMM_MKL	Benign	0.29	N
LIST_S2	Uncertain	0.87	D;D;D
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.34	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	M;.;.
MutationTaster	Benign	0.99	N;N;N
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-2.9	D;D;D
REVEL	Benign	0.12
Sift	Uncertain	0.0060	D;D;D
Sift4G	Uncertain	0.0050	D;D;D
Polyphen		1.0	D;.;.
Vest4		0.48
MutPred		0.27		Loss of disorder (P = 0.0016);.;.;
MVP		0.53
MPC		0.81
ClinPred		0.85	D
GERP RS		3.7
Varity_R		0.17
gMVP		0.60

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

LitVar

Other links and lift over

dbSNP: rs1450941482; hg19: chr1-153965346;