Genetic Variant ATF5:c.*22G>C (chr19-49933114-G-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001193646.2(ATF5):c.*22G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 30)

Consequence

ATF5
NM_001193646.2 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.392

Publications

24 publications found

Variant links:

Genes affected

ATF5 (HGNC:790): (activating transcription factor 5) Enables several functions, including DNA-binding transcription activator activity, RNA polymerase II-specific; RNA polymerase II transcription regulatory region sequence-specific DNA binding activity; and tubulin binding activity. Involved in several processes, including fat cell differentiation; regulation of cell cycle process; and regulation of transcription, DNA-templated. Located in centrosome; cytosol; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ATF5 links:

ENSG00000269179 (HGNC:):

ENSG00000269179 links:

MIR4751 (HGNC:41819): (microRNA 4751) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

MIR4751 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001193646.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ATF5	NM_001193646.2	MANE Select	c.*22G>C	3_prime_UTR	Exon 3 of 3	NP_001180575.1	Q9Y2D1
ATF5	NM_001290746.2		c.*22G>C	3_prime_UTR	Exon 3 of 3	NP_001277675.1	Q9Y2D1
ATF5	NM_012068.6		c.*22G>C	3_prime_UTR	Exon 4 of 4	NP_036200.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ATF5	ENST00000423777.7	TSL:1 MANE Select	c.*22G>C	3_prime_UTR	Exon 3 of 3	ENSP00000396954.1	Q9Y2D1
ENSG00000269179	ENST00000451973.1	TSL:2	n.*77+18777C>G	intron	N/A	ENSP00000391489.1	H7BZU6
ATF5	ENST00000595125.5	TSL:2	c.*22G>C	3_prime_UTR	Exon 4 of 4	ENSP00000470633.1	Q9Y2D1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

1.8

(source)

DANN

Benign

0.66

PhyloP100

0.39

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over