19-49932548-C-A

Variant names:

• chr19-49932548-C-A
• rs1159470845
• NM_001193646.2:c.305C>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001193646.2(ATF5):​c.305C>A​(p.Ala102Asp) variant causes a missense change. The variant allele was found at a frequency of 0.0000008 in 1,249,444 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A102G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 20)
  • Exomes 𝑓: 8.0e-7 (0 hom.)
• Consequence: ATF5 NM_001193646.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.45
• Publications: 0 publications found

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]

ENSG00000269179 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3782069).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATF5	NM_001193646.2	MANE Select	c.305C>A	p.Ala102Asp	missense	Exon 3 of 3	NP_001180575.1	Q9Y2D1
	ATF5	NM_001290746.2		c.305C>A	p.Ala102Asp	missense	Exon 3 of 3	NP_001277675.1	Q9Y2D1
	ATF5	NM_012068.6		c.305C>A	p.Ala102Asp	missense	Exon 4 of 4	NP_036200.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATF5	ENST00000423777.7	TSL:1 MANE Select	c.305C>A	p.Ala102Asp	missense	Exon 3 of 3	ENSP00000396954.1	Q9Y2D1
	ENSG00000269179	ENST00000451973.1	TSL:2	n.*77+19343G>T		intron	N/A	ENSP00000391489.1	H7BZU6
	ATF5	ENST00000595125.5	TSL:2	c.305C>A	p.Ala102Asp	missense	Exon 4 of 4	ENSP00000470633.1	Q9Y2D1

Frequencies

GnomAD3 genomes Cov.: 20

GnomAD4 exome AF: 8.00e-7 AC: 1 AN: 1249444 Hom.: 0 Cov.: 55 AF XY: 0.00 AC XY: 0 AN XY: 619472

African (AFR) AF: 0.00 AC: 0 AN: 27270

American (AMR) AF: 0.00 AC: 0 AN: 38324

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18420

East Asian (EAS) AF: 0.00 AC: 0 AN: 19014

South Asian (SAS) AF: 0.00 AC: 0 AN: 83940

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33094

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3898

European-Non Finnish (NFE) AF: 0.00000102 AC: 1 AN: 978802

Other (OTH) AF: 0.00 AC: 0 AN: 46682

GnomAD4 genome Cov.: 20

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.93
BayesDel_addAF	Benign	-0.054	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.046	T
Eigen	Uncertain	0.20
Eigen_PC	Benign	0.17
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.85	D
M_CAP	Uncertain	0.099	D
MetaRNN	Benign	0.38	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PhyloP100		6.4
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-0.31	N
REVEL	Benign	0.16
Sift	Uncertain	0.013	D
Sift4G	Benign	0.24	T
Polyphen		0.99	D
Vest4		0.46
MutPred		0.27		Gain of relative solvent accessibility (P = 0.09)
MVP		0.75
MPC		0.044
ClinPred		0.80	D
GERP RS		2.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.16
gMVP		0.55
Mutation Taster		=77/23	polymorphism

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

Other links and lift over

dbSNP: rs1159470845; hg19: chr19-50435805;