17-36949012-G-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012138.4(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 NM_012138.4 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.709
• Publications: 13 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: Benign. The variant received -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AATF	NM_012138.4	MANE Select	c.-114G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 12	NP_036270.1
	AATF	NM_012138.4	MANE Select	c.-114G>T		5_prime_UTR	Exon 1 of 12	NP_036270.1
	AATF	NM_001411094.1		c.-114G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 11	NP_001398023.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AATF	ENST00000619387.5	TSL:1 MANE Select	c.-114G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 12	ENSP00000477848.1
	AATF	ENST00000619387.5	TSL:1 MANE Select	c.-114G>T		5_prime_UTR	Exon 1 of 12	ENSP00000477848.1
	AATF	ENST00000679997.1		c.-114G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 12	ENSP00000505070.1

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

African (AFR) AF: 0.0898 AC: 1830 AN: 20388

American (AMR) AF: 0.00552 AC: 164 AN: 29722

Ashkenazi Jewish (ASJ) AF: 0.000220 AC: 4 AN: 18162

East Asian (EAS) AF: 0.0000312 AC: 1 AN: 32002

South Asian (SAS) AF: 0.000331 AC: 20 AN: 60402

European-Finnish (FIN) AF: 0.000170 AC: 6 AN: 35226

Middle Eastern (MID) AF: 0.00746 AC: 33 AN: 4426

European-Non Finnish (NFE) AF: 0.000221 AC: 141 AN: 638928

Other (OTH) AF: 0.00735 AC: 296 AN: 40292

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

African (AFR) AF: 0.0910 AC: 3780 AN: 41558

American (AMR) AF: 0.0102 AC: 156 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.000289 AC: 1 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000412 AC: 28 AN: 68008

Other (OTH) AF: 0.0151 AC: 32 AN: 2114

Alfa AF: 0.00 Hom.: 1117

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	4.4
DANN	Benign	0.55
PhyloP100		-0.71
PromoterAI		0.051	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Mutation Taster		=300/0	polymorphism (auto)

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: rs2306658; hg19: chr17-35306312;