Variant 1-154018976-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 3P and 6B. PM2PP2BP4_StrongBP6_Moderate

The ENST00000368559.8(NUP210L):c.4610T>C(p.Met1537Thr) 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 1,461,846 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

NUP210L
ENST00000368559.8 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.03

Variant links:

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]

NUP210L links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 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=0.03217724).

BP6

Variant 1-154018976-A-G is Benign according to our data. Variant chr1-154018976-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3203129.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NUP210L	NM_207308.3 linkuse as main transcript	c.4610T>C	p.Met1537Thr	missense_variant	33/40	ENST00000368559.8
NUP210L	XM_011510122.2 linkuse as main transcript	c.4478T>C	p.Met1493Thr	missense_variant	32/39

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NUP210L	ENST00000368559.8 linkuse as main transcript	c.4610T>C	p.Met1537Thr	missense_variant	33/40	5	NM_207308.3	P2	Q5VU65-1
NUP210L	ENST00000368553.5 linkuse as main transcript	c.1409T>C	p.Met470Thr	missense_variant	11/16	1		A2
NUP210L	ENST00000271854.3 linkuse as main transcript	c.4610T>C	p.Met1537Thr	missense_variant	33/38	5		A2	Q5VU65-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461846

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727228

show subpopulations

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.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 05, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.055

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.70

CADD

Benign

DANN

Benign

0.49

DEOGEN2

Benign

0.070

T;T;.

Eigen

Benign

-0.95

Eigen_PC

Benign

-0.65

FATHMM_MKL

Benign

0.081

LIST_S2

Benign

0.47

T;T;T

M_CAP

Benign

0.0030

MetaRNN

Benign

0.032

T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-1.5

N;.;N

MutationTaster

Benign

0.99

N;N;N

PrimateAI

Benign

0.24

PROVEAN

Benign

2.3

N;N;N

REVEL

Benign

0.020

Sift

Benign

1.0

T;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0

B;.;.

Vest4

0.26

MutPred

0.43

Loss of stability (P = 0.0989);.;Loss of stability (P = 0.0989);

MVP

0.25

MPC

0.33

ClinPred

0.036

GERP RS

2.7

Varity_R

0.035

gMVP

0.57

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over