Variant 7-75421608-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001099415.3(POM121C):c.2644A>G(p.Thr882Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00716 in 1,605,478 control chromosomes in the GnomAD database, including 284 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.022 ( 62 hom., cov: 32)

Exomes 𝑓: 0.0057 ( 222 hom. )

Consequence

POM121C
NM_001099415.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.57

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 Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0047879815).

BP6

Variant 7-75421608-T-C is Benign according to our data. Variant chr7-75421608-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2212045.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0217 (3250/150000) while in subpopulation AFR AF= 0.0338 (1360/40202). AF 95% confidence interval is 0.0323. There are 62 homozygotes in gnomad4. There are 1570 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 62 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POM121C	NM_001099415.3 link	c.2644A>G	p.Thr882Ala	missense_variant	13/15	ENST00000615331.5	NP_001092885.2	B4DET5B4DDR5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POM121C	ENST00000615331.5 link	c.2644A>G	p.Thr882Ala	missense_variant	13/15	1	NM_001099415.3	ENSP00000481575.1		A8CG34-2
POM121C	ENST00000607367.5 link	c.3370A>G	p.Thr1124Ala	missense_variant	11/13	5		ENSP00000476236.2		A8CG34-1

Frequencies

GnomAD3 genomes

AF:

0.0217

AC:

3253

AN:

149888

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0340

Gnomad AMI

AF:

0.0478

Gnomad AMR

AF:

0.0125

Gnomad ASJ

AF:

0.0220

Gnomad EAS

AF:

0.0162

Gnomad SAS

AF:

0.0158

Gnomad FIN

AF:

0.0329

Gnomad MID

AF:

0.00962

Gnomad NFE

AF:

0.0156

Gnomad OTH

AF:

0.0116

GnomAD3 exomes

AF:

0.00378

AC:

942

AN:

248890

Hom.:

AF XY:

0.00336

AC XY:

453

AN XY:

134900

show subpopulations

Gnomad AFR exome

AF:

0.0145

Gnomad AMR exome

AF:

0.00334

Gnomad ASJ exome

AF:

0.00230

Gnomad EAS exome

AF:

0.00619

Gnomad SAS exome

AF:

0.00311

Gnomad FIN exome

AF:

0.00154

Gnomad NFE exome

AF:

0.00266

Gnomad OTH exome

AF:

0.00593

GnomAD4 exome

AF:

0.00566

AC:

8242

AN:

1455478

Hom.:

222

Cov.:

AF XY:

0.00578

AC XY:

4185

AN XY:

724056

show subpopulations

Gnomad4 AFR exome

AF:

0.0175

Gnomad4 AMR exome

AF:

0.00471

Gnomad4 ASJ exome

AF:

0.00961

Gnomad4 EAS exome

AF:

0.00976

Gnomad4 SAS exome

AF:

0.00872

Gnomad4 FIN exome

AF:

0.0190

Gnomad4 NFE exome

AF:

0.00407

Gnomad4 OTH exome

AF:

0.00872

GnomAD4 genome

AF:

0.0217

AC:

3250

AN:

150000

Hom.:

Cov.:

AF XY:

0.0214

AC XY:

1570

AN XY:

73230

show subpopulations

Gnomad4 AFR

AF:

0.0338

Gnomad4 AMR

AF:

0.0125

Gnomad4 ASJ

AF:

0.0220

Gnomad4 EAS

AF:

0.0160

Gnomad4 SAS

AF:

0.0159

Gnomad4 FIN

AF:

0.0329

Gnomad4 NFE

AF:

0.0156

Gnomad4 OTH

AF:

0.0114

Alfa

AF:

0.00619

Hom.:

ExAC

AF:

0.000593

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 02, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.059

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.73

CADD

Benign

6.8

DANN

Benign

0.36

DEOGEN2

Benign

0.019

.;T

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.00038

LIST_S2

Benign

0.12

T;T

M_CAP

Benign

0.0087

MetaRNN

Benign

0.0048

T;T

MetaSVM

Benign

-0.96

PrimateAI

Benign

0.33

Sift4G

Benign

0.85

T;T

Polyphen

0.0

.;B

Vest4

0.11

MVP

0.030

ClinPred

0.0014

GERP RS

1.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.018

gMVP

0.26

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