Variant 7-75421824-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate

The NM_001099415.3(POM121C):c.2428G>C(p.Gly810Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 10/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

POM121C
NM_001099415.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.486

Variant links:

Genes affected

POM121C (HGNC:34005): (POM121 transmembrane nucleoporin C) 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 located in nuclear envelope. Predicted to be part of nuclear pore. [provided by Alliance of Genome Resources, Apr 2022]

POM121C links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), POM121C. . Trascript score misZ 4.3224 (greater than threshold 3.09). GenCC has associacion of gene with schizophrenia.

BP4

Computational evidence support a benign effect (MetaRNN=0.18953335).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POM121C	NM_001099415.3 linkuse as main transcript	c.2428G>C	p.Gly810Arg	missense_variant	13/15	ENST00000615331.5	NP_001092885.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POM121C	ENST00000615331.5 linkuse as main transcript	c.2428G>C	p.Gly810Arg	missense_variant	13/15	1	NM_001099415.3	ENSP00000481575	A2	A8CG34-2
POM121C	ENST00000607367.5 linkuse as main transcript	c.3154G>C	p.Gly1052Arg	missense_variant	11/13	5		ENSP00000476236	P4	A8CG34-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

6.86e-7

AC:

AN:

1457280

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

724798

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 08, 2023

The c.2428G>C (p.G810R) alteration is located in exon 13 (coding exon 10) of the POM121C gene. This alteration results from a G to C substitution at nucleotide position 2428, causing the glycine (G) at amino acid position 810 to be replaced by an arginine (R). 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

Uncertain

0.54

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.16

.;T

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.77

FATHMM_MKL

Benign

0.20

LIST_S2

Uncertain

0.87

D;D

M_CAP

Benign

0.017

MetaRNN

Benign

0.19

T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

0.97

N;N

PrimateAI

Benign

0.48

Sift4G

Benign

0.085

T;T

Polyphen

0.98

.;D

Vest4

0.38

MutPred

0.41

.;Loss of sheet (P = 0.0037);

MVP

0.35

ClinPred

0.78

GERP RS

-0.42

Varity_R

0.042

gMVP

0.33

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over