chr17-36949130-C-A

Variant names:

• chr17-36949130-C-A
• rs752205542
• NM_012138.4:c.5C>A

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM1 PM2

The NM_012138.4(AATF):​c.5C>A​(p.Ala2Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000702 in 1,424,248 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. A2G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: AATF NM_012138.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.44
• 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 4 ACMG points.

• PM1: In a modified_residue N-acetylalanine (size 0) in uniprot entity AATF_HUMAN
• PM2: Very rare variant in population databases, with high coverage

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.5C>A	p.Ala2Glu	missense	Exon 1 of 12	NP_036270.1	Q9NY61
	AATF	NM_001411094.1		c.5C>A	p.Ala2Glu	missense	Exon 1 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.5C>A	p.Ala2Glu	missense	Exon 1 of 12	ENSP00000477848.1	Q9NY61
	AATF	ENST00000905217.1		c.5C>A	p.Ala2Glu	missense	Exon 1 of 12	ENSP00000575276.1
	AATF	ENST00000953116.1		c.5C>A	p.Ala2Glu	missense	Exon 1 of 12	ENSP00000623175.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.02e-7 AC: 1 AN: 1424248 Hom.: 0 Cov.: 31 AF XY: 0.00000142 AC XY: 1 AN XY: 704816

African (AFR) AF: 0.00 AC: 0 AN: 32924

American (AMR) AF: 0.00 AC: 0 AN: 38142

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25306

East Asian (EAS) AF: 0.0000261 AC: 1 AN: 38282

South Asian (SAS) AF: 0.00 AC: 0 AN: 80976

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49330

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5706

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1094492

Other (OTH) AF: 0.00 AC: 0 AN: 59090

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Pathogenic	0.16	D
BayesDel_noAF	Uncertain	0.0
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.18	T
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Pathogenic	0.98	D
M_CAP	Benign	0.030	D
MetaRNN	Uncertain	0.50	T
MetaSVM	Benign	-0.59	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		3.4
PrimateAI	Uncertain	0.77	T
Sift4G	Uncertain	0.019	D
Polyphen		1.0	D
Vest4		0.42
MutPred		0.20		Gain of solvent accessibility (P = 0.0456)
MVP		0.53
ClinPred		0.96	D
GERP RS		5.0
PromoterAI		-0.11	Neutral
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.2
Varity_R		0.12
gMVP		0.45

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

dbSNP: rs752205542; hg19: chr17-35306430;