19-49932548-C-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001193646.2(ATF5):​c.305C>G​(p.Ala102Gly) 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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 20)
• Consequence: ATF5 NM_001193646.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.45

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34666157).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATF5	NM_001193646.2	c.305C>G	p.Ala102Gly	missense_variant	Exon 3 of 3	ENST00000423777.7	NP_001180575.1
ATF5	NM_001290746.2	c.305C>G	p.Ala102Gly	missense_variant	Exon 3 of 3		NP_001277675.1
ATF5	NM_012068.6	c.305C>G	p.Ala102Gly	missense_variant	Exon 4 of 4		NP_036200.2
ATF5	XM_011526629.4	c.305C>G	p.Ala102Gly	missense_variant	Exon 3 of 3		XP_011524931.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATF5	ENST00000423777.7	c.305C>G	p.Ala102Gly	missense_variant	Exon 3 of 3	1	NM_001193646.2	ENSP00000396954.1
ENSG00000269179	ENST00000451973.1	n.*77+19343G>C		intron_variant	Intron 2 of 2	2		ENSP00000391489.1

Frequencies

GnomAD3 genomes Cov.: 20

GnomAD4 exome Cov.: 55

GnomAD4 genome Cov.: 20

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 20, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.305C>G (p.A102G) alteration is located in exon 4 (coding exon 2) of the ATF5 gene. This alteration results from a C to G substitution at nucleotide position 305, causing the alanine (A) at amino acid position 102 to be replaced by a glycine (G). 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	Uncertain	0.40
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.051	T;T;.;.
Eigen	Benign	0.090
Eigen_PC	Benign	0.088
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.76	.;T;T;T
M_CAP	Benign	0.066	D
MetaRNN	Benign	0.35	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L;L;.;.
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-1.0	.;N;.;.
REVEL	Benign	0.13
Sift	Uncertain	0.010	.;D;.;.
Sift4G	Benign	0.33	T;T;D;D
Polyphen		0.90	P;P;.;.
Vest4		0.23
MutPred		0.25		Gain of methylation at K107 (P = 0.1363);Gain of methylation at K107 (P = 0.1363);Gain of methylation at K107 (P = 0.1363);Gain of methylation at K107 (P = 0.1363);
MVP		0.71
MPC		0.024
ClinPred		0.84	D
GERP RS		2.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.11
gMVP		0.26

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-50435805;