7-72930023-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001387691.1(POM121):​c.1187C>G​(p.Ser396Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000616 in 1,461,652 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

POM121
NM_001387691.1 missense

Scores

1
7
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.99
Variant links:
Genes affected
POM121 (HGNC:19702): (POM121 transmembrane nucleoporin) This gene encodes a transmembrane protein that localizes to the inner nuclear membrane and forms a core component of the nuclear pore complex, which mediates transport to and from the nucleus. The encoded protein may anchor this complex to the nuclear envelope. There are multiple related genes and pseudogenes for this gene on chromosomes 5, 7, 15, and 22. Alternatively spliced transcript variants encoding different isoforms have been observed. [provided by RefSeq, Jul 2013]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 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
POM121NM_001387691.1 linkc.1187C>G p.Ser396Cys missense_variant Exon 5 of 13 ENST00000434423.5 NP_001374620.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
POM121ENST00000434423.5 linkc.1187C>G p.Ser396Cys missense_variant Exon 5 of 13 5 NM_001387691.1 ENSP00000405562.2 Q96HA1-1
POM121ENST00000395270.5 linkc.392C>G p.Ser131Cys missense_variant Exon 8 of 16 1 ENSP00000378687.1 Q96HA1-3
POM121ENST00000627934.3 linkc.392C>G p.Ser131Cys missense_variant Exon 7 of 15 5 ENSP00000486504.1 Q96HA1-2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251168
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135736
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:
0.00
Gnomad NFE exome
AF:
0.00000881
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000616
AC:
9
AN:
1461652
Hom.:
0
Cov.:
31
AF XY:
0.00000550
AC XY:
4
AN XY:
727140
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:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000720
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000756
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Oct 26, 2021
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.392C>G (p.S131C) alteration is located in exon 7 (coding exon 4) of the POM121 gene. This alteration results from a C to G substitution at nucleotide position 392, causing the serine (S) at amino acid position 131 to be replaced by a cysteine (C). 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
0.14
BayesDel_addAF
Benign
-0.088
T
BayesDel_noAF
Benign
-0.36
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Benign
0.21
.;.;.;.;T
Eigen
Benign
-0.080
Eigen_PC
Benign
-0.20
FATHMM_MKL
Uncertain
0.84
D
LIST_S2
Benign
0.63
.;T;T;.;T
M_CAP
Benign
0.039
D
MetaRNN
Uncertain
0.66
D;D;D;D;D
MetaSVM
Benign
-0.77
T
MutationAssessor
Pathogenic
3.1
.;.;.;.;M
PrimateAI
Uncertain
0.56
T
PROVEAN
Uncertain
-3.9
D;.;D;D;D
REVEL
Benign
0.15
Sift
Uncertain
0.0040
D;.;D;D;D
Sift4G
Uncertain
0.0040
D;D;D;D;D
Polyphen
1.0
.;.;.;.;D
Vest4
0.76
MVP
0.055
ClinPred
0.83
D
GERP RS
3.2
Varity_R
0.21
gMVP
0.49

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.

Other links and lift over

dbSNP: rs137923425; hg19: chr7-72400561; API