Variant 12-108517040-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_007076.3(FICD):c.68G>A(p.Arg23His) variant causes a missense change. The variant allele was found at a frequency of 0.0000379 in 1,581,326 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000041 ( 0 hom. )

Consequence

FICD
NM_007076.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.26

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FICD	NM_007076.3 linkuse as main transcript	c.68G>A	p.Arg23His	missense_variant	2/3	ENST00000552695.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
FICD	ENST00000552695.6 linkuse as main transcript	c.68G>A	p.Arg23His	missense_variant	2/3	1	NM_007076.3	P1
FICD	ENST00000361549.2 linkuse as main transcript	c.68G>A	p.Arg23His	missense_variant	2/3	1
FICD	ENST00000552758.1 linkuse as main transcript	c.68G>A	p.Arg23His	missense_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000385

AC:

AN:

233864

Hom.:

AF XY:

0.0000473

AC XY:

AN XY:

126906

show subpopulations

Gnomad AFR exome

AF:

0.0000632

Gnomad AMR exome

AF:

0.0000690

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000552

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000406

AC:

AN:

1429114

Hom.:

Cov.:

AF XY:

0.0000353

AC XY:

AN XY:

708878

show subpopulations

Gnomad4 AFR exome

AF:

0.0000309

Gnomad4 AMR exome

AF:

0.0000501

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000485

Gnomad4 OTH exome

AF:

0.0000340

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152212

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000113

Hom.:

Bravo

AF:

0.0000302

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 01, 2024

The c.68G>A (p.R23H) alteration is located in exon 2 (coding exon 1) of the FICD gene. This alteration results from a G to A substitution at nucleotide position 68, causing the arginine (R) at amino acid position 23 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.031

BayesDel_noAF

Benign

-0.10

Cadd

Uncertain

Dann

Pathogenic

1.0

DEOGEN2

Benign

0.049

T;.;.

Eigen

Uncertain

0.59

Eigen_PC

Uncertain

0.55

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.86

D;D;D

M_CAP

Benign

0.013

MetaRNN

Uncertain

0.66

D;D;D

MetaSVM

Benign

-0.48

MutationAssessor

Benign

1.9

L;.;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-0.64

N;N;N

REVEL

Uncertain

0.38

Sift

Uncertain

0.015

D;D;D

Sift4G

Uncertain

0.038

D;D;D

Polyphen

1.0

D;.;.

Vest4

0.66

MutPred

0.43

Gain of catalytic residue at W21 (P = 5e-04);Gain of catalytic residue at W21 (P = 5e-04);Gain of catalytic residue at W21 (P = 5e-04);

MVP

0.85

MPC

0.93

ClinPred

0.32

GERP RS

5.3

Varity_R

0.17

gMVP

0.54

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