Variant 6-27310176-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_033482.4(POM121L2):c.1995C>A(p.Phe665Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000198 in 1,551,960 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00021 ( 0 hom. )

Consequence

POM121L2
NM_033482.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.434

Variant links:

Genes affected

POM121L2 (HGNC:13973): (POM121 transmembrane nucleoporin like 2) Predicted to enable nuclear localization sequence binding activity. Predicted to be a structural constituent of nuclear pore. Predicted to be involved in RNA export from nucleus and protein import into nucleus. Predicted to be part of nuclear pore. [provided by Alliance of Genome Resources, Apr 2022]

POM121L2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.115866095).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POM121L2	NM_033482.4 linkuse as main transcript	c.1995C>A	p.Phe665Leu	missense_variant	1/1	ENST00000444565.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POM121L2	ENST00000444565.2 linkuse as main transcript	c.1995C>A	p.Phe665Leu	missense_variant	1/1		NM_033482.4	P1
POM121L2	ENST00000429945.1 linkuse as main transcript	c.216+921C>A		intron_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0000920

AC:

AN:

152242

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.000176

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000824

AC:

AN:

157820

Hom.:

AF XY:

0.0000600

AC XY:

AN XY:

83372

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.000118

Gnomad NFE exome

AF:

0.000179

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000210

AC:

294

AN:

1399718

Hom.:

Cov.:

AF XY:

0.000184

AC XY:

127

AN XY:

690352

show subpopulations

Gnomad4 AFR exome

AF:

0.0000316

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:

0.0000405

Gnomad4 NFE exome

AF:

0.000265

Gnomad4 OTH exome

AF:

0.0000861

GnomAD4 genome

AF:

0.0000920

AC:

AN:

152242

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.0000241

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:

0.000176

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000270

Hom.:

Bravo

AF:

0.0000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 10, 2023

The c.1995C>A (p.F665L) alteration is located in exon 1 (coding exon 1) of the POM121L2 gene. This alteration results from a C to A substitution at nucleotide position 1995, causing the phenylalanine (F) at amino acid position 665 to be replaced by a leucine (L). 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

Pathogenic

0.65

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.63

Cadd

Benign

9.4

Dann

Benign

0.93

DEOGEN2

Benign

0.16

Eigen

Benign

-0.92

Eigen_PC

Benign

-0.96

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.39

M_CAP

Benign

0.0029

MetaRNN

Benign

0.12

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.6

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.38

PROVEAN

Uncertain

-3.2

REVEL

Benign

0.053

Sift

Benign

0.17

Sift4G

Benign

0.88

Vest4

0.18

MutPred

0.49

Loss of catalytic residue at F665 (P = 0.0034);

MVP

0.030

ClinPred

0.045

GERP RS

-0.53

Varity_R

0.12

gMVP

0.27

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over