ENST00000619387:c.-114G>T

Variant names:

• chr17-36949012-G-T
• rs2306658
• ENST00000619387:c.-114G>T

Variant summary

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

The ENST00000619387(AATF):​c.-114G>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0063 in 1,031,794 control chromosomes in the GnomAD database, including 282 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 0.026 (199 hom., cov: 35)
  • Exomes 𝑓: 0.0028 (83 hom.)
• Consequence: AATF ENST00000619387 5_prime_UTR_premature_start_codon_gain
• 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=-0.75).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0885 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AATF	NM_012138.4	c.-114G>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 12	ENST00000619387.5	NP_036270.1
AATF	NM_012138.4	c.-114G>T		5_prime_UTR_variant	Exon 1 of 12	ENST00000619387.5	NP_036270.1

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0262 AC: 3986 AN: 152128 Hom.: 200 Cov.: 35

Gnomad AFR AF: 0.0908

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0102

Gnomad ASJ AF: 0.000289

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000412

Gnomad OTH AF: 0.0153

GnomAD4 exome AF: 0.00284 AC: 2495 AN: 879548 Hom.: 83 Cov.: 12 AF XY: 0.00245 AC XY: 1083 AN XY: 442030

Gnomad4 AFR exome AF: 0.0898

Gnomad4 AMR exome AF: 0.00552

Gnomad4 ASJ exome AF: 0.000220

Gnomad4 EAS exome AF: 0.0000312

Gnomad4 SAS exome AF: 0.000331

Gnomad4 FIN exome AF: 0.000170

Gnomad4 NFE exome AF: 0.000221

Gnomad4 OTH exome AF: 0.00735

GnomAD4 genome AF: 0.0263 AC: 4002 AN: 152246 Hom.: 199 Cov.: 35 AF XY: 0.0252 AC XY: 1879 AN XY: 74426

Gnomad4 AFR AF: 0.0910

Gnomad4 AMR AF: 0.0102

Gnomad4 ASJ AF: 0.000289

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000412

Gnomad4 OTH AF: 0.0151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	4.4
DANN	Benign	0.55
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;