12-14424354-G-A

Variant summary

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

The NM_018179.5(ATF7IP):c.439G>A(p.Gly147Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000981 in 1,613,982 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0011 ( 3 hom., cov: 32)

Exomes 𝑓: 0.00097 ( 21 hom. )

Consequence

ATF7IP
NM_018179.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.841

Variant links:

Genes affected

ATF7IP (HGNC:20092): (activating transcription factor 7 interacting protein) ATF7IP is a multifunctional nuclear protein that associates with heterochromatin. It can act as a transcriptional coactivator or corepressor depending upon its binding partners (summary by Liu et al., 2009 [PubMed 19106100]).[supplied by OMIM, Nov 2010]

ATF7IP 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=0.0028405786).

BP6

Variant 12-14424354-G-A is Benign according to our data. Variant chr12-14424354-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 781696.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATF7IP	NM_018179.5 linkuse as main transcript	c.439G>A	p.Gly147Arg	missense_variant	2/15	ENST00000261168.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATF7IP	ENST00000261168.9 linkuse as main transcript	c.439G>A	p.Gly147Arg	missense_variant	2/15	5	NM_018179.5	P5	Q6VMQ6-1

Frequencies

GnomAD3 genomes

AF:

0.00113

AC:

172

AN:

152096

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.0369

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000559

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00174

AC:

438

AN:

251352

Hom.:

AF XY:

0.00177

AC XY:

240

AN XY:

135850

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000578

Gnomad ASJ exome

AF:

0.0368

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000475

Gnomad OTH exome

AF:

0.00163

GnomAD4 exome

AF:

0.000965

AC:

1411

AN:

1461886

Hom.:

Cov.:

AF XY:

0.000938

AC XY:

682

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.0344

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000314

Gnomad4 OTH exome

AF:

0.00253

GnomAD4 genome

AF:

0.00113

AC:

172

AN:

152096

Hom.:

Cov.:

AF XY:

0.00108

AC XY:

AN XY:

74292

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.0369

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000559

Gnomad4 OTH

AF:

0.00191

Alfa

AF:

0.00213

Hom.:

Bravo

AF:

0.00115

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00256

AC:

ExAC

AF:

0.00153

AC:

186

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000872

EpiControl

AF:

0.00107

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

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.57

Cadd

Benign

Dann

Uncertain

0.97

DEOGEN2

Benign

0.012

T;.;.;T;T;.;T;T;T;T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.40

LIST_S2

Benign

0.63

T;T;T;.;T;T;T;T;T;T;.

M_CAP

Benign

0.025

MetaRNN

Benign

0.0028

T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.63

N;N;N;.;.;.;.;.;.;.;N

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.020

N;N;N;N;N;N;N;N;N;N;N

REVEL

Benign

0.035

Sift

Uncertain

0.014

D;D;D;D;D;D;T;D;T;D;D

Sift4G

Benign

0.13

T;T;T;T;T;T;T;T;T;T;T

Polyphen

0.0070

B;B;.;.;.;.;.;.;.;.;B

Vest4

0.059

MutPred

0.34

Loss of catalytic residue at V148 (P = 0.0307);Loss of catalytic residue at V148 (P = 0.0307);Loss of catalytic residue at V148 (P = 0.0307);Loss of catalytic residue at V148 (P = 0.0307);Loss of catalytic residue at V148 (P = 0.0307);.;Loss of catalytic residue at V148 (P = 0.0307);Loss of catalytic residue at V148 (P = 0.0307);Loss of catalytic residue at V148 (P = 0.0307);Loss of catalytic residue at V148 (P = 0.0307);Loss of catalytic residue at V148 (P = 0.0307);

MVP

0.13

MPC

0.71

ClinPred

0.026

GERP RS

-0.085

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.12

gMVP

0.080

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