Genetic Variant POM121:p.Asp329Glu (chr7-72926928-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001387691.1(POM121):c.987C>A(p.Asp329Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000192 in 1,461,670 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

POM121
NM_001387691.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.110

Publications

0 publications found

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]

POM121 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.040917367).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001387691.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
POM121	NM_001387691.1	MANE Select	c.987C>A	p.Asp329Glu	missense	Exon 3 of 13	NP_001374620.1	Q96HA1-1
POM121	NM_001387692.1		c.987C>A	p.Asp329Glu	missense	Exon 3 of 12	NP_001374621.1
POM121	NM_001387693.1		c.987C>A	p.Asp329Glu	missense	Exon 3 of 10	NP_001374622.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
POM121	ENST00000434423.5	TSL:5 MANE Select	c.987C>A	p.Asp329Glu	missense	Exon 3 of 13	ENSP00000405562.2	Q96HA1-1
POM121	ENST00000395270.5	TSL:1	c.192C>A	p.Asp64Glu	missense	Exon 6 of 16	ENSP00000378687.1	Q96HA1-3
POM121	ENST00000897647.1		c.987C>A	p.Asp329Glu	missense	Exon 3 of 12	ENSP00000567706.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000159

AC:

AN:

251180

AF XY:

0.00000737

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000353

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000192

AC:

AN:

1461670

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

727146

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33472

American (AMR)

AF:

0.00

AC:

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86250

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.0000252

AC:

AN:

1111840

Other (OTH)

AF:

0.00

AC:

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.441

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.035

Eigen

Benign

-0.69

Eigen_PC

Benign

-0.70

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.67

M_CAP

Benign

0.0044

MetaRNN

Benign

0.041

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.9

PhyloP100

-0.11

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-0.76

REVEL

Benign

0.060

Sift

Benign

0.57

Sift4G

Uncertain

0.052

Polyphen

0.042

Vest4

0.22

MutPred

0.34

Loss of loop (P = 0.4412)

MVP

0.014

ClinPred

0.28

GERP RS

0.016

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.067

gMVP

0.19

Mutation Taster

=89/11

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over