Variant chr14-105314317-A-G 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_001243127.3(PACS2):c.-83+13338A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0144 in 151,212 control chromosomes in the GnomAD database, including 59 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.014 ( 59 hom., cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PACS2
NM_001243127.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.768

Variant links:

Genes affected

PACS2 (HGNC:23794): (phosphofurin acidic cluster sorting protein 2) Predicted to enable transmembrane transporter binding activity. Involved in endoplasmic reticulum calcium ion homeostasis; mitochondrion-endoplasmic reticulum membrane tethering; and protein localization to plasma membrane. Acts upstream of or within protein localization to phagophore assembly site. Located in endoplasmic reticulum and mitochondrion. Implicated in developmental and epileptic encephalopathy 66. [provided by Alliance of Genome Resources, Apr 2022]

PACS2 links:

BRF1 (HGNC:11551): (BRF1 RNA polymerase III transcription initiation factor subunit) This gene encodes one of the three subunits of the RNA polymerase III transcription factor complex. This complex plays a central role in transcription initiation by RNA polymerase III on genes encoding tRNA, 5S rRNA, and other small structural RNAs. The gene product belongs to the TF2B family. Several alternatively spliced variants encoding different isoforms, that function at different promoters transcribed by RNA polymerase III, have been identified. [provided by RefSeq, Jun 2011]

BRF1 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 (BayesDel_noAF=-0.87).

BP6

Variant 14-105314317-A-G is Benign according to our data. Variant chr14-105314317-A-G is described in ClinVar as [Benign]. Clinvar id is 1251079.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0144 (2180/151212) while in subpopulation AFR AF= 0.0504 (2073/41158). AF 95% confidence interval is 0.0486. There are 59 homozygotes in gnomad4. There are 1003 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 2180 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Protein	UniProt
PACS2	NM_001243127.3 linkuse as main transcript	c.-83+13338A>G	intron_variant	NP_001230056.1	Q86VP3-4Q8N7J0
BRF1	NM_001242786.2 linkuse as main transcript	c.-162+1005T>C	intron_variant	NP_001229715.1	Q92994-8
BRF1	NM_001242787.2 linkuse as main transcript	c.-162+1005T>C	intron_variant	NP_001229716.1	Q92994-7

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	Protein	UniProt
PACS2	ENST00000430725.6 linkuse as main transcript	c.-83+13338A>G	intron_variant	1	ENSP00000393524.2	Q86VP3-4
BRF1	ENST00000440513.7 linkuse as main transcript	c.-162+1005T>C	intron_variant	2	ENSP00000388877.3	Q92994-8
BRF1	ENST00000327359.7 linkuse as main transcript	c.-162+1005T>C	intron_variant	2	ENSP00000329029.3	Q92994-7
BRF1	ENST00000550692.1 linkuse as main transcript	c.-162+1025T>C	intron_variant	4	ENSP00000448823.1	F8VXJ4

Frequencies

GnomAD3 genomes

AF:

0.0144

AC:

2182

AN:

151098

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0505

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00532

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000295

Gnomad OTH

AF:

0.0120

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

110

Hom.:

AF XY:

0.00

AC XY:

AN XY:

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 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0144

AC:

2180

AN:

151212

Hom.:

Cov.:

AF XY:

0.0136

AC XY:

1003

AN XY:

73916

show subpopulations

Gnomad4 AFR

AF:

0.0504

Gnomad4 AMR

AF:

0.00518

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000295

Gnomad4 OTH

AF:

0.0119

Alfa

AF:

0.0107

Hom.:

Bravo

AF:

0.0160

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 22, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

3.6

DANN

Benign

0.87

Splicing

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