Variant 7-75421912-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_001099415.3(POM121C):c.2340G>A(p.Thr780=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00116 in 1,613,146 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0012 ( 9 hom. )

Consequence

POM121C
NM_001099415.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.98

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 7-75421912-C-T is Benign according to our data. Variant chr7-75421912-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2657609.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-1.98 with no splicing effect.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00117 (1709/1460738) while in subpopulation MID AF= 0.0219 (124/5660). AF 95% confidence interval is 0.0188. There are 9 homozygotes in gnomad4_exome. There are 931 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POM121C	NM_001099415.3 linkuse as main transcript	c.2340G>A	p.Thr780=	synonymous_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.2340G>A	p.Thr780=	synonymous_variant	13/15	1	NM_001099415.3	ENSP00000481575	A2	A8CG34-2
POM121C	ENST00000607367.5 linkuse as main transcript	c.3066G>A	p.Thr1022=	synonymous_variant	11/13	5		ENSP00000476236	P4	A8CG34-1

Frequencies

GnomAD3 genomes

AF:

0.00107

AC:

163

AN:

152290

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00242

Gnomad ASJ

AF:

0.00518

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.00289

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00101

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00163

AC:

408

AN:

250030

Hom.:

AF XY:

0.00188

AC XY:

255

AN XY:

135424

show subpopulations

Gnomad AFR exome

AF:

0.000187

Gnomad AMR exome

AF:

0.00217

Gnomad ASJ exome

AF:

0.00469

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00314

Gnomad FIN exome

AF:

0.0000463

Gnomad NFE exome

AF:

0.00140

Gnomad OTH exome

AF:

0.00459

GnomAD4 exome

AF:

0.00117

AC:

1709

AN:

1460738

Hom.:

Cov.:

AF XY:

0.00128

AC XY:

931

AN XY:

726686

show subpopulations

Gnomad4 AFR exome

AF:

0.000538

Gnomad4 AMR exome

AF:

0.00219

Gnomad4 ASJ exome

AF:

0.00467

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00306

Gnomad4 FIN exome

AF:

0.0000568

Gnomad4 NFE exome

AF:

0.000859

Gnomad4 OTH exome

AF:

0.00206

GnomAD4 genome

AF:

0.00107

AC:

163

AN:

152408

Hom.:

Cov.:

AF XY:

0.00106

AC XY:

AN XY:

74534

show subpopulations

Gnomad4 AFR

AF:

0.000144

Gnomad4 AMR

AF:

0.00242

Gnomad4 ASJ

AF:

0.00518

Gnomad4 EAS

AF:

0.000578

Gnomad4 SAS

AF:

0.00310

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.00101

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00155

Hom.:

Bravo

AF:

0.00117

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.00284

EpiControl

AF:

0.00207

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2022

POM121C: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.48

DANN

Benign

0.67

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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