rs3213764

Variant names:

• chr12-14434367-A-C
• NM_018179.5:c.1589A>C

Your query was ambiguous. Multiple possible variants found:

• chr12-14434367-A-C
• chr12-14434367-A-G
• chr12-14434367-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>C​(p.Lys530Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000014 in 1,432,148 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• 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 rank	MANE	Protein	UniProt
ATF7IP	NM_018179.5	c.1589A>C	p.Lys530Thr	missense_variant	Exon 3 of 15	ENST00000261168.9	NP_060649.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATF7IP	ENST00000261168.9	c.1589A>C	p.Lys530Thr	missense_variant	Exon 3 of 15	5	NM_018179.5	ENSP00000261168.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000140 AC: 2 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: 0.0000387

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: 0.0000168

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.013	T;.;.;.;T
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.82	T;T;T;T;.
M_CAP	Benign	0.043	D
MetaRNN	Uncertain	0.44	T;T;T;T;T
MetaSVM	Benign	-0.80	T
MutationAssessor	Benign	1.9	L;.;.;.;L
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-1.2	N;N;N;N;N
REVEL	Benign	0.069
Sift	Uncertain	0.0050	D;D;D;D;D
Sift4G	Uncertain	0.029	D;T;D;D;D
Polyphen		0.97	D;D;.;.;D
Vest4		0.28
MutPred		0.20		Gain of phosphorylation at K530 (P = 0.0054);.;.;.;Gain of phosphorylation at K530 (P = 0.0054);
MVP		0.39
MPC		0.46
ClinPred		0.87	D
GERP RS		4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.11
gMVP		0.059

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-14587301;