Variant 7-75418889-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001099415.3(POM121C):c.2871G>A(p.Ser957Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0155 in 1,610,208 control chromosomes in the GnomAD database, including 248 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 23 hom., cov: 31)

Exomes 𝑓: 0.016 ( 225 hom. )

Consequence

POM121C
NM_001099415.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.50

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 7-75418889-C-T is Benign according to our data. Variant chr7-75418889-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 779917.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.5 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0131 (1996/152166) while in subpopulation NFE AF= 0.0164 (1115/67990). AF 95% confidence interval is 0.0156. There are 23 homozygotes in gnomad4. There are 1048 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 23 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POM121C	NM_001099415.3 link	c.2871G>A	p.Ser957Ser	synonymous_variant	15/15	ENST00000615331.5	NP_001092885.2	B4DET5B4DDR5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
POM121C	ENST00000615331.5 link	c.2871G>A	p.Ser957Ser	synonymous_variant	15/15	1	NM_001099415.3	ENSP00000481575.1	A8CG34-2
POM121C	ENST00000607367.5 link	c.3597G>A	p.Ser1199Ser	synonymous_variant	13/13	5		ENSP00000476236.2	A8CG34-1
POM121C	ENST00000614583.1 link	n.1971G>A		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.0131

AC:

1996

AN:

152048

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00273

Gnomad AMI

AF:

0.0263

Gnomad AMR

AF:

0.00877

Gnomad ASJ

AF:

0.00750

Gnomad EAS

AF:

0.0143

Gnomad SAS

AF:

0.00685

Gnomad FIN

AF:

0.0430

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0164

Gnomad OTH

AF:

0.00955

GnomAD3 exomes

AF:

0.0147

AC:

3525

AN:

239818

Hom.:

AF XY:

0.0150

AC XY:

1957

AN XY:

130512

show subpopulations

Gnomad AFR exome

AF:

0.00202

Gnomad AMR exome

AF:

0.00511

Gnomad ASJ exome

AF:

0.00862

Gnomad EAS exome

AF:

0.0149

Gnomad SAS exome

AF:

0.00692

Gnomad FIN exome

AF:

0.0397

Gnomad NFE exome

AF:

0.0170

Gnomad OTH exome

AF:

0.0150

GnomAD4 exome

AF:

0.0158

AC:

22973

AN:

1458042

Hom.:

225

Cov.:

AF XY:

0.0154

AC XY:

11188

AN XY:

725398

show subpopulations

Gnomad4 AFR exome

AF:

0.00237

Gnomad4 AMR exome

AF:

0.00491

Gnomad4 ASJ exome

AF:

0.00725

Gnomad4 EAS exome

AF:

0.00978

Gnomad4 SAS exome

AF:

0.00700

Gnomad4 FIN exome

AF:

0.0388

Gnomad4 NFE exome

AF:

0.0166

Gnomad4 OTH exome

AF:

0.0152

GnomAD4 genome

AF:

0.0131

AC:

1996

AN:

152166

Hom.:

Cov.:

AF XY:

0.0141

AC XY:

1048

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.00272

Gnomad4 AMR

AF:

0.00876

Gnomad4 ASJ

AF:

0.00750

Gnomad4 EAS

AF:

0.0143

Gnomad4 SAS

AF:

0.00685

Gnomad4 FIN

AF:

0.0430

Gnomad4 NFE

AF:

0.0164

Gnomad4 OTH

AF:

0.00945

Alfa

AF:

0.00770

Hom.:

Bravo

AF:

0.0102

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 23, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

8.8

DANN

Benign

0.92

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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