19-49932548-C-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001193646.2(ATF5):​c.305C>T​(p.Ala102Val) variant causes a missense change. 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. 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)
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21150374).

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>T	p.Ala102Val	missense	Exon 3 of 3	NP_001180575.1	Q9Y2D1
	ATF5	NM_001290746.2		c.305C>T	p.Ala102Val	missense	Exon 3 of 3	NP_001277675.1	Q9Y2D1
	ATF5	NM_012068.6		c.305C>T	p.Ala102Val	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>T	p.Ala102Val	missense	Exon 3 of 3	ENSP00000396954.1	Q9Y2D1
	ENSG00000269179	ENST00000451973.1	TSL:2	n.*77+19343G>A		intron	N/A	ENSP00000391489.1	H7BZU6
	ATF5	ENST00000595125.5	TSL:2	c.305C>T	p.Ala102Val	missense	Exon 4 of 4	ENSP00000470633.1	Q9Y2D1

Frequencies

GnomAD3 genomes Cov.: 20

GnomAD4 exome Cov.: 55

GnomAD4 genome Cov.: 20

Alfa AF: 0.000224 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.046	T
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.17
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.050	D
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L
PhyloP100		6.4
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-0.030	N
REVEL	Benign	0.10
Sift	Benign	0.45	T
Sift4G	Benign	0.17	T
Polyphen		0.056	B
Vest4		0.28
MutPred		0.30		Gain of methylation at K107 (P = 0.1063)
MVP		0.60
MPC		0.024
ClinPred		0.66	D
GERP RS		2.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.033
gMVP		0.30
Mutation Taster		=90/10	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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;