NM_012138.4:c.160G>C

Variant names:

• chr17-36950282-G-C
• NM_012138.4:c.160G>C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_012138.4(AATF):​c.160G>C​(p.Gly54Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: AATF NM_012138.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.54
• Publications: 0 publications found

Genes affected

AATF (HGNC:19235): (apoptosis antagonizing transcription factor) The protein encoded by this gene was identified on the basis of its interaction with MAP3K12/DLK, a protein kinase known to be involved in the induction of cell apoptosis. This gene product contains a leucine zipper, which is a characteristic motif of transcription factors, and was shown to exhibit strong transactivation activity when fused to Gal4 DNA binding domain. Overexpression of this gene interfered with MAP3K12 induced apoptosis. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.753

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012138.4. 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
	AATF	NM_012138.4	MANE Select	c.160G>C	p.Gly54Arg	missense	Exon 2 of 12	NP_036270.1	Q9NY61
	AATF	NM_001411094.1		c.160G>C	p.Gly54Arg	missense	Exon 2 of 11	NP_001398023.1	A0A7P0TAR0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AATF	ENST00000619387.5	TSL:1 MANE Select	c.160G>C	p.Gly54Arg	missense	Exon 2 of 12	ENSP00000477848.1	Q9NY61
	AATF	ENST00000905217.1		c.160G>C	p.Gly54Arg	missense	Exon 2 of 12	ENSP00000575276.1
	AATF	ENST00000953116.1		c.160G>C	p.Gly54Arg	missense	Exon 2 of 12	ENSP00000623175.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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	0.28
BayesDel_addAF	Uncertain	0.032	T
BayesDel_noAF	Benign	-0.19
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.33	T
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Uncertain	0.93	D
M_CAP	Benign	0.0083	T
MetaRNN	Pathogenic	0.75	D
MetaSVM	Benign	-0.80	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		3.5
PrimateAI	Uncertain	0.53	T
Sift4G	Benign	0.079	T
Polyphen		0.99	D
Vest4		0.65
MutPred		0.48		Gain of MoRF binding (P = 0.0174)
MVP		0.67
ClinPred		0.95	D
GERP RS		4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.39
gMVP		0.10

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

Other links and lift over

hg19: chr17-35307582;