19-49930984-G-T

Position:

• chr19-49930984-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001193646.2(ATF5):​c.134G>T​(p.Gly45Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ATF5 NM_001193646.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.81

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATF5	NM_001193646.2	c.134G>T	p.Gly45Val	missense_variant	2/3	ENST00000423777.7	NP_001180575.1
ATF5	NM_001290746.2	c.134G>T	p.Gly45Val	missense_variant	2/3		NP_001277675.1
ATF5	NM_012068.6	c.134G>T	p.Gly45Val	missense_variant	3/4		NP_036200.2
ATF5	XM_011526629.4	c.134G>T	p.Gly45Val	missense_variant	2/3		XP_011524931.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATF5	ENST00000423777.7	c.134G>T	p.Gly45Val	missense_variant	2/3	1	NM_001193646.2	ENSP00000396954	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 26, 2022

The c.134G>T (p.G45V) alteration is located in exon 3 (coding exon 1) of the ATF5 gene. This alteration results from a G to T substitution at nucleotide position 134, causing the glycine (G) at amino acid position 45 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Uncertain	0.076	D
BayesDel_noAF	Benign	-0.13
CADD	Benign	23
DANN	Benign	0.96
DEOGEN2	Benign	0.051	T;T;.;.;.
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.71	.;T;T;T;T
M_CAP	Benign	0.023	T
MetaRNN	Uncertain	0.54	D;D;D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N;N;.;.;.
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-1.6	.;N;.;.;.
REVEL	Benign	0.22
Sift	Benign	0.12	.;T;.;.;.
Sift4G	Benign	0.51	T;T;D;T;T
Polyphen		1.0	D;D;.;.;.
Vest4		0.75
MutPred		0.37		Loss of disorder (P = 0.0411);Loss of disorder (P = 0.0411);Loss of disorder (P = 0.0411);Loss of disorder (P = 0.0411);Loss of disorder (P = 0.0411);
MVP		0.72
MPC		0.15
ClinPred		0.86	D
GERP RS		4.7
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		3.0
Varity_R		0.15
gMVP		0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-50434241;