dbSNP rs559447703: POM121:p.Pro3Ala (chr7-72925128-C-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001387691.1(POM121):c.7C>G(p.Pro3Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000102 in 1,278,302 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P3S) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

POM121
NM_001387691.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.28

Publications

1 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:

ENSG00000272843 (HGNC:):

ENSG00000272843 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.29421934).

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.7C>G	p.Pro3Ala	missense	Exon 1 of 13	NP_001374620.1	Q96HA1-1
POM121	NM_001387692.1		c.7C>G	p.Pro3Ala	missense	Exon 1 of 12	NP_001374621.1
POM121	NM_001387693.1		c.7C>G	p.Pro3Ala	missense	Exon 1 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.7C>G	p.Pro3Ala	missense	Exon 1 of 13	ENSP00000405562.2	Q96HA1-1
POM121	ENST00000395270.5	TSL:1	c.-151-1134C>G		intron	N/A	ENSP00000378687.1	Q96HA1-3
POM121	ENST00000897647.1		c.7C>G	p.Pro3Ala	missense	Exon 1 of 12	ENSP00000567706.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000102

AC:

AN:

1278302

Hom.:

Cov.:

AF XY:

0.0000127

AC XY:

AN XY:

627954

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24856

American (AMR)

AF:

0.00

AC:

AN:

16000

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19338

East Asian (EAS)

AF:

0.00

AC:

AN:

29186

South Asian (SAS)

AF:

0.00

AC:

AN:

63676

European-Finnish (FIN)

AF:

0.00

AC:

AN:

31216

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3776

European-Non Finnish (NFE)

AF:

0.0000106

AC:

AN:

1037268

Other (OTH)

AF:

0.0000377

AC:

AN:

52986

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.529

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.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.044

BayesDel_noAF

Benign

-0.30

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0070

Eigen

Uncertain

0.51

Eigen_PC

Uncertain

0.45

FATHMM_MKL

Benign

0.58

LIST_S2

Benign

0.53

M_CAP

Uncertain

0.21

MetaRNN

Benign

0.29

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

PhyloP100

2.3

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-1.3

REVEL

Benign

0.10

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.27

MutPred

0.14

Loss of loop (P = 0.0075)

MVP

0.13

ClinPred

0.94

GERP RS

3.8

PromoterAI

0.080

Neutral

(source)

Varity_R

0.34

Mutation Taster

=90/10

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