12-14424018-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_018179.5(ATF7IP):c.103G>A(p.Glu35Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ATF7IP NM_018179.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.94

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2742325).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATF7IP	NM_018179.5	c.103G>A	p.Glu35Lys	missense_variant	2/15	ENST00000261168.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATF7IP	ENST00000261168.9	c.103G>A	p.Glu35Lys	missense_variant	2/15	5	NM_018179.5	P5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 03, 2021

The c.103G>A (p.E35K) alteration is located in exon 2 (coding exon 1) of the ATF7IP gene. This alteration results from a G to A substitution at nucleotide position 103, causing the glutamic acid (E) at amino acid position 35 to be replaced by a lysine (K). 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	Uncertain	0.48
BayesDel_addAF	Benign	-0.053	T
BayesDel_noAF	Benign	-0.31
Cadd	Uncertain	25
Dann	Pathogenic	1.0
DEOGEN2	Benign	0.096	T;T;.;.;T;T;T;.;T;T;T;T;.;T;T;.;T
Eigen	Uncertain	0.66
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.87	D;D;D;D;.;D;D;D;D;D;D;D;D;D;D;D;.
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.27	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	1.1	L;.;L;L;.;.;.;.;.;.;.;.;.;.;.;.;L
MutationTaster	Benign	0.99	D;D;D;D;D
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-0.71	N;N;N;N;D;D;D;N;D;D;D;D;D;N;D;D;N
REVEL	Benign	0.22
Sift	Uncertain	0.0050	D;D;D;D;D;D;D;D;T;D;D;D;D;D;D;D;D
Sift4G	Uncertain	0.017	D;D;T;D;D;D;T;D;T;D;D;D;T;D;T;T;D
Polyphen		0.93	P;.;D;.;.;.;.;.;.;.;.;.;.;.;.;.;P
Vest4		0.17
MutPred		0.34		Gain of MoRF binding (P = 0.0015);Gain of MoRF binding (P = 0.0015);Gain of MoRF binding (P = 0.0015);Gain of MoRF binding (P = 0.0015);Gain of MoRF binding (P = 0.0015);Gain of MoRF binding (P = 0.0015);Gain of MoRF binding (P = 0.0015);.;Gain of MoRF binding (P = 0.0015);Gain of MoRF binding (P = 0.0015);Gain of MoRF binding (P = 0.0015);Gain of MoRF binding (P = 0.0015);Gain of MoRF binding (P = 0.0015);Gain of MoRF binding (P = 0.0015);Gain of MoRF binding (P = 0.0015);Gain of MoRF binding (P = 0.0015);Gain of MoRF binding (P = 0.0015);
MVP		0.46
MPC		0.53
ClinPred		0.74	D
GERP RS		5.7
Varity_R		0.096
gMVP		0.074

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

Other links and lift over

dbSNP: rs1941685722; hg19: chr12-14576952;