Variant 12-108518622-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_007076.3(FICD):c.524A>C(p.Lys175Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00635 in 1,614,206 control chromosomes in the GnomAD database, including 50 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0050 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0065 ( 46 hom. )

Consequence

FICD
NM_007076.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.14

Variant links:

Genes affected

FICD (HGNC:18416): (FIC domain protein adenylyltransferase) Enables several functions, including ATP binding activity; Hsp70 protein binding activity; and chaperone binding activity. Involved in protein adenylylation; regulation of IRE1-mediated unfolded protein response; and response to endoplasmic reticulum stress. Is integral component of endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Apr 2022]

FICD links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0087251365).

BP6

Variant 12-108518622-A-C is Benign according to our data. Variant chr12-108518622-A-C is described in ClinVar as [Benign]. Clinvar id is 791633.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FICD	NM_007076.3 linkuse as main transcript	c.524A>C	p.Lys175Thr	missense_variant	3/3	ENST00000552695.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
FICD	ENST00000552695.6 linkuse as main transcript	c.524A>C	p.Lys175Thr	missense_variant	3/3	1	NM_007076.3	P1
FICD	ENST00000361549.2 linkuse as main transcript	c.*261A>C		3_prime_UTR_variant	3/3	1
FICD	ENST00000549641.1 linkuse as main transcript	c.153+1349A>C		intron_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00497

AC:

756

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00133

Gnomad AMI

AF:

0.0318

Gnomad AMR

AF:

0.00413

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00226

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00817

Gnomad OTH

AF:

0.00574

GnomAD3 exomes

AF:

0.00448

AC:

1127

AN:

251478

Hom.:

AF XY:

0.00455

AC XY:

619

AN XY:

135912

show subpopulations

Gnomad AFR exome

AF:

0.000984

Gnomad AMR exome

AF:

0.00390

Gnomad ASJ exome

AF:

0.00188

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00124

Gnomad FIN exome

AF:

0.00286

Gnomad NFE exome

AF:

0.00720

Gnomad OTH exome

AF:

0.00619

GnomAD4 exome

AF:

0.00650

AC:

9501

AN:

1461878

Hom.:

Cov.:

AF XY:

0.00642

AC XY:

4671

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.00108

Gnomad4 AMR exome

AF:

0.00402

Gnomad4 ASJ exome

AF:

0.00207

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00133

Gnomad4 FIN exome

AF:

0.00331

Gnomad4 NFE exome

AF:

0.00771

Gnomad4 OTH exome

AF:

0.00576

GnomAD4 genome

AF:

0.00497

AC:

757

AN:

152328

Hom.:

Cov.:

AF XY:

0.00443

AC XY:

330

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.00132

Gnomad4 AMR

AF:

0.00412

Gnomad4 ASJ

AF:

0.00317

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.00226

Gnomad4 NFE

AF:

0.00819

Gnomad4 OTH

AF:

0.00568

Alfa

AF:

0.00685

Hom.:

Bravo

AF:

0.00470

TwinsUK

AF:

0.00944

AC:

ALSPAC

AF:

0.00441

AC:

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.00744

AC:

ExAC

AF:

0.00453

AC:

550

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00567

EpiControl

AF:

0.00753

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

Invitae

Jun 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Uncertain

-0.030

Cadd

Benign

Dann

Benign

0.95

DEOGEN2

Benign

0.076

Eigen

Benign

-0.12

Eigen_PC

Benign

-0.027

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.045

MetaRNN

Benign

0.0087

MetaSVM

Benign

-0.53

MutationAssessor

Benign

1.9

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-2.0

REVEL

Uncertain

0.39

Sift

Benign

0.21

Sift4G

Benign

0.18

Polyphen

0.073

Vest4

0.45

MVP

0.79

MPC

0.35

ClinPred

0.023

GERP RS

5.6

Varity_R

0.55

gMVP

0.51

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