Variant chrX-107167739-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_017681.3(NUP62CL):c.104C>T(p.Thr35Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000835 in 1,197,105 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T35A) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.0000083 ( 0 hom. 3 hem. )

Consequence

NUP62CL
NM_017681.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.54

Variant links:

Genes affected

NUP62CL (HGNC:25960): (nucleoporin 62 C-terminal like) This gene encodes a protein containing a domain found in nucleoporins which are glycoproteins found in nuclear pore complexes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2011]

NUP62CL links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.063439995).

BS2

High Hemizygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NUP62CL	NM_017681.3 linkuse as main transcript	c.104C>T	p.Thr35Ile	missense_variant	4/9	ENST00000372466.8
NUP62CL	NR_033676.2 linkuse as main transcript	n.312C>T		non_coding_transcript_exon_variant	3/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NUP62CL	ENST00000372466.8 linkuse as main transcript	c.104C>T	p.Thr35Ile	missense_variant	4/9	1	NM_017681.3	P1	Q9H1M0-1
NUP62CL	ENST00000421752.1 linkuse as main transcript	c.104C>T	p.Thr35Ile	missense_variant	3/6	2
NUP62CL	ENST00000484614.5 linkuse as main transcript	c.104C>T	p.Thr35Ile	missense_variant, NMD_transcript_variant	3/7	2			Q9H1M0-2

Frequencies

GnomAD3 genomes

AF:

0.00000891

AC:

AN:

112225

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34393

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000830

AC:

AN:

1084825

Hom.:

Cov.:

AF XY:

0.00000855

AC XY:

AN XY:

350717

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:

0.0000108

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000891

AC:

AN:

112280

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34458

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000188

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000249

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.093

T;.

FATHMM_MKL

Benign

0.23

LIST_S2

Benign

0.41

T;T

M_CAP

Benign

0.014

MetaRNN

Benign

0.063

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

N;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.42

PROVEAN

Uncertain

-3.4

D;D

REVEL

Benign

0.045

Sift

Benign

0.081

T;T

Sift4G

Uncertain

0.046

D;.

Polyphen

0.037

B;.

Vest4

0.16

MVP

0.12

MPC

0.23

ClinPred

0.081

GERP RS

2.8

Varity_R

0.10

gMVP

0.40

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over