1-154023201-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2 PP2 BP4_Moderate

The ENST00000368559.8(NUP210L):c.4219A>G(p.Thr1407Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,768 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: NUP210L ENST00000368559.8 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.36

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 1 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=0.2448332).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NUP210L	NM_207308.3	c.4219A>G	p.Thr1407Ala	missense_variant	31/40	ENST00000368559.8
NUP210L	XM_011510122.2	c.4087A>G	p.Thr1363Ala	missense_variant	30/39

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NUP210L	ENST00000368559.8	c.4219A>G	p.Thr1407Ala	missense_variant	31/40	5	NM_207308.3	P2
NUP210L	ENST00000368553.5	c.1018A>G	p.Thr340Ala	missense_variant	9/16	1		A2
NUP210L	ENST00000271854.3	c.4219A>G	p.Thr1407Ala	missense_variant	31/38	5		A2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461768 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727200

Gnomad4 AFR exome AF: 0.000149

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

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

Oct 03, 2022

The c.4219A>G (p.T1407A) alteration is located in exon 31 (coding exon 31) of the NUP210L gene. This alteration results from a A to G substitution at nucleotide position 4219, causing the threonine (T) at amino acid position 1407 to be replaced by an alanine (A). 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	0.076
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
Cadd	Benign	21
Dann	Uncertain	0.99
DEOGEN2	Benign	0.22	T;T;.
Eigen	Benign	-0.12
Eigen_PC	Benign	0.014
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.59	T;T;T
M_CAP	Benign	0.0072	T
MetaRNN	Benign	0.24	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.4	M;.;M
MutationTaster	Benign	0.83	N;N;N
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-2.7	D;D;D
REVEL	Benign	0.075
Sift	Benign	0.061	T;T;T
Sift4G	Benign	0.11	T;T;T
Polyphen		0.0010	B;.;.
Vest4		0.27
MutPred		0.45		Loss of stability (P = 0.0543);.;Loss of stability (P = 0.0543);
MVP		0.54
MPC		0.29
ClinPred		0.84	D
GERP RS		4.2
Varity_R		0.12
gMVP		0.53

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: rs1651663591; hg19: chr1-153995677;