GeneBe

chr6-27309698-G-A

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_033482.4(POM121L2):​c.2473C>T​(p.Gln825*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000357 in 1,399,420 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000036 ( 0 hom. )

Consequence

POM121L2
NM_033482.4 stop_gained

Scores

2
5

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.14

Publications

0 publications found
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]

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
POM121L2NM_033482.4 linkc.2473C>T p.Gln825* stop_gained Exon 1 of 1 ENST00000444565.2 NP_258443.2 Q96KW2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
POM121L2ENST00000444565.2 linkc.2473C>T p.Gln825* stop_gained Exon 1 of 1 6 NM_033482.4 ENSP00000392726.1 Q96KW2
POM121L2ENST00000429945.1 linkc.216+1399C>T intron_variant Intron 1 of 1 3 ENSP00000415181.1 H7C418

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000357
AC:
5
AN:
1399420
Hom.:
0
Cov.:
63
AF XY:
0.00000290
AC XY:
2
AN XY:
690212
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
31598
American (AMR)
AF:
0.00
AC:
0
AN:
35704
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25182
East Asian (EAS)
AF:
0.00
AC:
0
AN:
35738
South Asian (SAS)
AF:
0.00
AC:
0
AN:
79236
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
49276
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5698
European-Non Finnish (NFE)
AF:
0.00000463
AC:
5
AN:
1078984
Other (OTH)
AF:
0.00
AC:
0
AN:
58004
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.495
Heterozygous variant carriers
0
1
2
2
3
4
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.34
D
BayesDel_noAF
Pathogenic
0.25
CADD
Pathogenic
34
DANN
Benign
0.96
Eigen
Benign
0.029
Eigen_PC
Benign
-0.34
FATHMM_MKL
Benign
0.056
N
PhyloP100
1.1
Vest4
0.049
GERP RS
1.8
Mutation Taster
=60/140
disease causing

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

Other links and lift over

dbSNP: rs772578613; hg19: chr6-27277477; API