Genetic Variant NM_001193646.2:c.615C>T (chr19-49932858-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_001193646.2(ATF5):c.615C>T(p.Thr205Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0299 in 1,612,610 control chromosomes in the GnomAD database, including 980 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 0.036 ( 137 hom., cov: 28)

Exomes 𝑓: 0.029 ( 843 hom. )

Consequence

ATF5
NM_001193646.2 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.16

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 made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP7

Synonymous conserved (PhyloP=2.16 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0605 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATF5	NM_001193646.2 link	c.615C>T	p.Thr205Thr	synonymous_variant	Exon 3 of 3	ENST00000423777.7	NP_001180575.1	Q9Y2D1A0A024QZG3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATF5	ENST00000423777.7 link	c.615C>T	p.Thr205Thr	synonymous_variant	Exon 3 of 3	1	NM_001193646.2	ENSP00000396954.1		Q9Y2D1
ENSG00000269179	ENST00000451973.1 link	n.*77+19033G>A		intron_variant	Intron 2 of 2	2		ENSP00000391489.1		H7BZU6

Frequencies

GnomAD3 genomes

AF:

0.0361

AC:

5475

AN:

151720

Hom.:

136

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0628

Gnomad AMI

AF:

0.00879

Gnomad AMR

AF:

0.0232

Gnomad ASJ

AF:

0.0248

Gnomad EAS

AF:

0.000966

Gnomad SAS

AF:

0.0659

Gnomad FIN

AF:

0.0116

Gnomad MID

AF:

0.0665

Gnomad NFE

AF:

0.0280

Gnomad OTH

AF:

0.0336

GnomAD3 exomes

AF:

0.0285

AC:

7051

AN:

247706

Hom.:

174

AF XY:

0.0300

AC XY:

4020

AN XY:

134142

show subpopulations

Gnomad AFR exome

AF:

0.0607

Gnomad AMR exome

AF:

0.0150

Gnomad ASJ exome

AF:

0.0243

Gnomad EAS exome

AF:

0.000329

Gnomad SAS exome

AF:

0.0632

Gnomad FIN exome

AF:

0.00907

Gnomad NFE exome

AF:

0.0273

Gnomad OTH exome

AF:

0.0268

GnomAD4 exome

AF:

0.0293

AC:

42818

AN:

1460772

Hom.:

843

Cov.:

AF XY:

0.0304

AC XY:

22103

AN XY:

726608

show subpopulations

Gnomad4 AFR exome

AF:

0.0607

Gnomad4 AMR exome

AF:

0.0158

Gnomad4 ASJ exome

AF:

0.0256

Gnomad4 EAS exome

AF:

0.000176

Gnomad4 SAS exome

AF:

0.0626

Gnomad4 FIN exome

AF:

0.0100

Gnomad4 NFE exome

AF:

0.0283

Gnomad4 OTH exome

AF:

0.0291

GnomAD4 genome

AF:

0.0360

AC:

5470

AN:

151838

Hom.:

137

Cov.:

AF XY:

0.0355

AC XY:

2637

AN XY:

74184

show subpopulations

Gnomad4 AFR

AF:

0.0625

Gnomad4 AMR

AF:

0.0232

Gnomad4 ASJ

AF:

0.0248

Gnomad4 EAS

AF:

0.000968

Gnomad4 SAS

AF:

0.0651

Gnomad4 FIN

AF:

0.0116

Gnomad4 NFE

AF:

0.0280

Gnomad4 OTH

AF:

0.0351

Alfa

AF:

0.0321

Hom.:

Bravo

AF:

0.0365

Asia WGS

AF:

0.0430

AC:

150

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

1.5

DANN

Benign

0.57

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over