12-14434367-A-T

Variant summary

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

The NM_018179.5(ATF7IP):c.1589A>T(p.Lys530Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K530R) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ATF7IP NM_018179.5 missense
• Clinical Significance: Not reported in ClinVar
• 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 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
ATF7IP	NM_018179.5	c.1589A>T	p.Lys530Ile	missense_variant	3/15	ENST00000261168.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATF7IP	ENST00000261168.9	c.1589A>T	p.Lys530Ile	missense_variant	3/15	5	NM_018179.5	P5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1432148 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 713762

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.084	T
BayesDel_noAF	Benign	-0.36
Cadd	Benign	23
Dann	Uncertain	1.0
DEOGEN2	Benign	0.012	T;.;.;.;T
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.80	T;T;T;T;.
M_CAP	Benign	0.060	D
MetaRNN	Uncertain	0.55	D;D;D;D;D
MetaSVM	Benign	-0.79	T
MutationAssessor	Benign	1.9	L;.;.;.;L
MutationTaster	Benign	0.0026	P;P;P;P;P
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-1.9	N;N;N;N;N
REVEL	Benign	0.087
Sift	Uncertain	0.0060	D;D;D;D;D
Sift4G	Uncertain	0.0080	D;D;D;D;D
Polyphen		1.0	D;D;.;.;D
Vest4		0.40
MutPred		0.19		Gain of helix (P = 0.005);.;.;.;Gain of helix (P = 0.005);
MVP		0.44
MPC		0.77
ClinPred		0.92	D
GERP RS		4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.14
gMVP		0.086

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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;