Genetic Variant NM_001193646.2:c.255C>A (chr19-49932498-C-A) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001193646.2(ATF5):c.255C>A(p.Pro85Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00496 in 1,605,344 control chromosomes in the GnomAD database, including 412 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.024 ( 201 hom., cov: 26)

Exomes 𝑓: 0.0030 ( 211 hom. )

Consequence

ATF5
NM_001193646.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.60

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant 19-49932498-C-A is Benign according to our data. Variant chr19-49932498-C-A is described in ClinVar as [Benign]. Clinvar id is 781515.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.61 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0827 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATF5	NM_001193646.2 link	c.255C>A	p.Pro85Pro	synonymous_variant	Exon 3 of 3	ENST00000423777.7	NP_001180575.1	Q9Y2D1A0A024QZG3
ATF5	NM_001290746.2 link	c.255C>A	p.Pro85Pro	synonymous_variant	Exon 3 of 3		NP_001277675.1	Q9Y2D1A0A024QZG3
ATF5	NM_012068.6 link	c.255C>A	p.Pro85Pro	synonymous_variant	Exon 4 of 4		NP_036200.2	Q9Y2D1A0A024QZG3
ATF5	XM_011526629.4 link	c.255C>A	p.Pro85Pro	synonymous_variant	Exon 3 of 3		XP_011524931.1	Q9Y2D1A0A024QZG3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATF5	ENST00000423777.7 link	c.255C>A	p.Pro85Pro	synonymous_variant	Exon 3 of 3	1	NM_001193646.2	ENSP00000396954.1		Q9Y2D1
ENSG00000269179	ENST00000451973.1 link	n.*77+19393G>T		intron_variant	Intron 2 of 2	2		ENSP00000391489.1		H7BZU6

Frequencies

GnomAD3 genomes

AF:

0.0235

AC:

3511

AN:

149252

Hom.:

202

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0849

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00713

Gnomad ASJ

AF:

0.000289

Gnomad EAS

AF:

0.000197

Gnomad SAS

AF:

0.000839

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000251

Gnomad OTH

AF:

0.0161

GnomAD3 exomes

AF:

0.00743

AC:

1827

AN:

245788

Hom.:

AF XY:

0.00553

AC XY:

742

AN XY:

134092

show subpopulations

Gnomad AFR exome

AF:

0.103

Gnomad AMR exome

AF:

0.00460

Gnomad ASJ exome

AF:

0.000301

Gnomad EAS exome

AF:

0.000110

Gnomad SAS exome

AF:

0.00184

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000145

Gnomad OTH exome

AF:

0.00434

GnomAD4 exome

AF:

0.00304

AC:

4431

AN:

1455984

Hom.:

211

Cov.:

AF XY:

0.00260

AC XY:

1884

AN XY:

724436

show subpopulations

Gnomad4 AFR exome

AF:

0.106

Gnomad4 AMR exome

AF:

0.00513

Gnomad4 ASJ exome

AF:

0.000422

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.00174

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000100

Gnomad4 OTH exome

AF:

0.00660

GnomAD4 genome

AF:

0.0236

AC:

3532

AN:

149360

Hom.:

201

Cov.:

AF XY:

0.0223

AC XY:

1626

AN XY:

72934

show subpopulations

Gnomad4 AFR

AF:

0.0851

Gnomad4 AMR

AF:

0.00712

Gnomad4 ASJ

AF:

0.000289

Gnomad4 EAS

AF:

0.000197

Gnomad4 SAS

AF:

0.000839

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000251

Gnomad4 OTH

AF:

0.0164

Alfa

AF:

0.00810

Hom.:

Asia WGS

AF:

0.00693

AC:

AN:

3476

EpiCase

AF:

0.000164

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 20, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

0.64

DANN

Benign

0.51

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over