rs3213764

chr12-14434367-A-Gchr12-14434367-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_018179.5(ATF7IP):c.1589A>G(p.Lys530Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.46 in 1,571,092 control chromosomes in the GnomAD database, including 170,778 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.43 (14742 hom., cov: 33)
  • Exomes 𝑓: 0.46 (156036 hom.)
• Consequence: ATF7IP NM_018179.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.11

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.3941526E-4).
• BP6: Variant 12-14434367-A-G is Benign according to our data. Variant chr12-14434367-A-G is described in ClinVar as [Benign]. Clinvar id is 1271269.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.58 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATF7IP	NM_018179.5	c.1589A>G	p.Lys530Arg	missense_variant	3/15	ENST00000261168.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATF7IP	ENST00000261168.9	c.1589A>G	p.Lys530Arg	missense_variant	3/15	5	NM_018179.5	P5

Frequencies

GnomAD3 genomes AF: 0.428 AC: 64993 AN: 151964 Hom.: 14741 Cov.: 33

Gnomad AFR AF: 0.280

Gnomad AMI AF: 0.435

Gnomad AMR AF: 0.378

Gnomad ASJ AF: 0.541

Gnomad EAS AF: 0.599

Gnomad SAS AF: 0.445

Gnomad FIN AF: 0.606

Gnomad MID AF: 0.417

Gnomad NFE AF: 0.480

Gnomad OTH AF: 0.434

GnomAD3 exomes AF: 0.465 AC: 113212 AN: 243266 Hom.: 27272 AF XY: 0.471 AC XY: 61932 AN XY: 131614

Gnomad AFR exome AF: 0.269

Gnomad AMR exome AF: 0.381

Gnomad ASJ exome AF: 0.526

Gnomad EAS exome AF: 0.586

Gnomad SAS exome AF: 0.434

Gnomad FIN exome AF: 0.599

Gnomad NFE exome AF: 0.477

Gnomad OTH exome AF: 0.451

GnomAD4 exome AF: 0.463 AC: 657043 AN: 1419010 Hom.: 156036 Cov.: 28 AF XY: 0.465 AC XY: 328899 AN XY: 707682

Gnomad4 AFR exome AF: 0.258

Gnomad4 AMR exome AF: 0.377

Gnomad4 ASJ exome AF: 0.520

Gnomad4 EAS exome AF: 0.618

Gnomad4 SAS exome AF: 0.444

Gnomad4 FIN exome AF: 0.593

Gnomad4 NFE exome AF: 0.461

Gnomad4 OTH exome AF: 0.456

GnomAD4 genome AF: 0.427 AC: 65003 AN: 152082 Hom.: 14742 Cov.: 33 AF XY: 0.434 AC XY: 32229 AN XY: 74342

Gnomad4 AFR AF: 0.280

Gnomad4 AMR AF: 0.378

Gnomad4 ASJ AF: 0.541

Gnomad4 EAS AF: 0.598

Gnomad4 SAS AF: 0.446

Gnomad4 FIN AF: 0.606

Gnomad4 NFE AF: 0.481

Gnomad4 OTH AF: 0.436

Alfa AF: 0.469 Hom.: 35342

Bravo AF: 0.402

TwinsUK AF: 0.458 AC: 1697

ALSPAC AF: 0.470 AC: 1813

ESP6500AA AF: 0.297 AC: 1310

ESP6500EA AF: 0.487 AC: 4184

ExAC AF: 0.471 AC: 57130

Asia WGS AF: 0.461 AC: 1601 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 28, 2020

This variant is associated with the following publications: (PMID: 23359319) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.60	T
BayesDel_noAF	Benign	-0.49
Cadd	Benign	21
Dann	Uncertain	1.0
DEOGEN2	Benign	0.013	T;.;.;.;T
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.59	T;T;T;T;.
MetaRNN	Benign	0.00014	T;T;T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.9	L;.;.;.;L
MutationTaster	Benign	0.027	P;P;P;P;P
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.62	N;N;N;N;N
REVEL	Benign	0.049
Sift	Uncertain	0.020	D;T;D;D;D
Sift4G	Uncertain	0.056	T;T;D;T;T
Polyphen		0.97	D;D;.;.;D
Vest4		0.057
MPC		0.31
ClinPred		0.014	T
GERP RS		4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.071
gMVP		0.024

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

Other links and lift over

dbSNP: rs3213764; hg19: chr12-14587301; COSMIC: COSV53766209;