NM_012138.4:c.-114G>C

Variant names:

• chr17-36949012-G-C
• rs2306658
• NM_012138.4:c.-114G>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012138.4(AATF):​c.-114G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.504 in 1,029,984 control chromosomes in the GnomAD database, including 141,271 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.40 (15163 hom., cov: 35)
  • Exomes 𝑓: 0.52 (126108 hom.)
• Consequence: AATF NM_012138.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.709

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.563 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AATF	NM_012138.4	c.-114G>C		5_prime_UTR_variant	Exon 1 of 12	ENST00000619387.5	NP_036270.1
AATF	NM_001411094.1	c.-114G>C		5_prime_UTR_variant	Exon 1 of 11		NP_001398023.1
AATF	XM_047435748.1	c.-114G>C		5_prime_UTR_variant	Exon 1 of 5		XP_047291704.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AATF	ENST00000619387	c.-114G>C		5_prime_UTR_variant	Exon 1 of 12	1	NM_012138.4	ENSP00000477848.1

Frequencies

GnomAD3 genomes AF: 0.399 AC: 60664 AN: 152116 Hom.: 15175 Cov.: 35

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.541

Gnomad AMR AF: 0.333

Gnomad ASJ AF: 0.590

Gnomad EAS AF: 0.192

Gnomad SAS AF: 0.400

Gnomad FIN AF: 0.555

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.568

Gnomad OTH AF: 0.440

GnomAD4 exome AF: 0.523 AC: 458882 AN: 877750 Hom.: 126108 Cov.: 12 AF XY: 0.522 AC XY: 230283 AN XY: 441242

Gnomad4 AFR exome AF: 0.100

Gnomad4 AMR exome AF: 0.268

Gnomad4 ASJ exome AF: 0.583

Gnomad4 EAS exome AF: 0.220

Gnomad4 SAS exome AF: 0.413

Gnomad4 FIN exome AF: 0.540

Gnomad4 NFE exome AF: 0.573

Gnomad4 OTH exome AF: 0.492

GnomAD4 genome AF: 0.398 AC: 60632 AN: 152234 Hom.: 15163 Cov.: 35 AF XY: 0.394 AC XY: 29324 AN XY: 74420

Gnomad4 AFR AF: 0.109

Gnomad4 AMR AF: 0.333

Gnomad4 ASJ AF: 0.590

Gnomad4 EAS AF: 0.191

Gnomad4 SAS AF: 0.399

Gnomad4 FIN AF: 0.555

Gnomad4 NFE AF: 0.568

Gnomad4 OTH AF: 0.434

Alfa AF: 0.362 Hom.: 1117

Bravo AF: 0.370

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	4.3
DANN	Benign	0.45
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

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

LitVar

Other links and lift over

dbSNP: rs2306658; hg19: chr17-35306312;