12-14424484-C-T

Variant names:

• chr12-14424484-C-T
• NM_018179.5:c.569C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018179.5(ATF7IP):​c.569C>T​(p.Thr190Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,772 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: ATF7IP NM_018179.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.74
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06121868).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018179.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATF7IP	NM_018179.5	MANE Select	c.569C>T	p.Thr190Ile	missense	Exon 2 of 15	NP_060649.3
	ATF7IP	NM_181352.2		c.593C>T	p.Thr198Ile	missense	Exon 2 of 15	NP_851997.1	Q6VMQ6-4
	ATF7IP	NM_001388179.1		c.593C>T	p.Thr198Ile	missense	Exon 2 of 15	NP_001375108.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATF7IP	ENST00000261168.9	TSL:5 MANE Select	c.569C>T	p.Thr190Ile	missense	Exon 2 of 15	ENSP00000261168.4	Q6VMQ6-1
	ATF7IP	ENST00000544627.5	TSL:1	c.593C>T	p.Thr198Ile	missense	Exon 2 of 15	ENSP00000440440.1	Q6VMQ6-4
	ATF7IP	ENST00000540793.5	TSL:1	c.569C>T	p.Thr190Ile	missense	Exon 1 of 14	ENSP00000444589.1	Q6VMQ6-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461772 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727198

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111916

Other (OTH) AF: 0.0000166 AC: 1 AN: 60392

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.82
DANN	Benign	0.96
DEOGEN2	Benign	0.0061	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.042	N
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.061	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.34	N
PhyloP100		-1.7
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.22	N
REVEL	Benign	0.055
Sift	Benign	0.18	T
Sift4G	Benign	0.32	T
Polyphen		0.0010	B
Vest4		0.026
MutPred		0.22		Loss of phosphorylation at T190 (P = 0.0326)
MVP		0.14
MPC		0.17
ClinPred		0.22	T
GERP RS		-1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.020
gMVP		0.033
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

hg19: chr12-14577418;