Genetic Variant POM121:p.Thr272Ser (chr7-72926432-C-G) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4

The NM_001387691.1(POM121):c.815C>G(p.Thr272Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000682 in 1,613,890 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 1 hom., cov: 32)

Exomes 𝑓: 0.000070 ( 1 hom. )

Consequence

POM121
NM_001387691.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.28

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.30346894).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POM121	NM_001387691.1 link	c.815C>G	p.Thr272Ser	missense_variant	Exon 2 of 13	ENST00000434423.5	NP_001374620.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
POM121	ENST00000434423.5 link	c.815C>G	p.Thr272Ser	missense_variant	Exon 2 of 13	5	NM_001387691.1	ENSP00000405562.2	Q96HA1-1
POM121	ENST00000395270.5 link	c.20C>G	p.Thr7Ser	missense_variant	Exon 5 of 16	1		ENSP00000378687.1	Q96HA1-3
POM121	ENST00000627934.3 link	c.20C>G	p.Thr7Ser	missense_variant	Exon 4 of 15	5		ENSP00000486504.1	Q96HA1-2

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000143

AC:

AN:

251114

Hom.:

AF XY:

0.000199

AC XY:

AN XY:

135728

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:

0.00118

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000705

AC:

103

AN:

1461672

Hom.:

Cov.:

AF XY:

0.0000976

AC XY:

AN XY:

727146

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:

0.00112

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.0000828

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152218

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ExAC

AF:

0.000157

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 21, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.20C>G (p.T7S) alteration is located in exon 4 (coding exon 1) of the POM121 gene. This alteration results from a C to G substitution at nucleotide position 20, causing the threonine (T) at amino acid position 7 to be replaced by a serine (S). 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

0.88

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.37

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.25

.;.;.;.;T

Eigen

Uncertain

0.42

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.79

.;T;T;.;T

M_CAP

Benign

0.025

MetaRNN

Benign

0.30

T;T;T;T;T

MetaSVM

Benign

-0.86

MutationAssessor

Uncertain

2.4

.;.;.;.;M

PrimateAI

Uncertain

0.61

PROVEAN

Uncertain

-3.3

D;.;D;D;D

REVEL

Benign

0.20

Sift

Uncertain

0.0090

D;.;D;D;T

Sift4G

Uncertain

0.046

D;D;D;D;T

Polyphen

0.98

.;.;.;.;D

Vest4

0.71

MutPred

0.54

.;.;.;.;Gain of disorder (P = 0.0292);

MVP

0.061

ClinPred

0.99

GERP RS

3.7

Varity_R

0.27

gMVP

0.41

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