1-154001832-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP2

The ENST00000368559.8(NUP210L):c.5084C>T(p.Ala1695Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,878 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: NUP210L ENST00000368559.8 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.01

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, NUP210L

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NUP210L	NM_207308.3	c.5084C>T	p.Ala1695Val	missense_variant	36/40	ENST00000368559.8
NUP210L	XM_011510122.2	c.4952C>T	p.Ala1651Val	missense_variant	35/39

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NUP210L	ENST00000368559.8	c.5084C>T	p.Ala1695Val	missense_variant	36/40	5	NM_207308.3	P2
NUP210L	ENST00000368553.5	c.1730-6652C>T		intron_variant		1		A2
NUP210L	ENST00000271854.3	c.4931-6652C>T		intron_variant		5		A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461878 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727240

Gnomad4 AFR exome AF: 0.00

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

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

Sep 01, 2021

The c.5084C>T (p.A1695V) alteration is located in exon 36 (coding exon 36) of the NUP210L gene. This alteration results from a C to T substitution at nucleotide position 5084, causing the alanine (A) at amino acid position 1695 to be replaced by a valine (V). 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	Uncertain	0.42
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
Cadd	Uncertain	23
Dann	Uncertain	1.0
DEOGEN2	Uncertain	0.50	T
Eigen	Benign	0.047
Eigen_PC	Benign	0.032
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.014	T
MetaRNN	Uncertain	0.55	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M
MutationTaster	Benign	1.0	D;D;N
PrimateAI	Uncertain	0.52	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.16
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.012	D
Polyphen		0.95	P
Vest4		0.44
MutPred		0.72		Gain of sheet (P = 0.0344);
MVP		0.58
MPC		0.83
ClinPred		0.96	D
GERP RS		2.9
Varity_R		0.13
gMVP		0.83

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-153974308;