rs34877198

Positions:

• chr19-49932741-C-G
• chr19-49932741-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001193646.2(ATF5):​c.498C>G​(p.Cys166Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 26)
• Consequence: ATF5 NM_001193646.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.655

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.766

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATF5	NM_001193646.2	c.498C>G	p.Cys166Trp	missense_variant	3/3	ENST00000423777.7	NP_001180575.1
ATF5	NM_001290746.2	c.498C>G	p.Cys166Trp	missense_variant	3/3		NP_001277675.1
ATF5	NM_012068.6	c.498C>G	p.Cys166Trp	missense_variant	4/4		NP_036200.2
ATF5	XM_011526629.4	c.498C>G	p.Cys166Trp	missense_variant	3/3		XP_011524931.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATF5	ENST00000423777.7	c.498C>G	p.Cys166Trp	missense_variant	3/3	1	NM_001193646.2	ENSP00000396954.1
ENSG00000269179	ENST00000451973.1	n.*77+19150G>C		intron_variant		2		ENSP00000391489.1
ATF5	ENST00000595125.5	c.498C>G	p.Cys166Trp	missense_variant	4/4	2		ENSP00000470633.1

Frequencies

GnomAD3 genomes Cov.: 26

GnomAD4 exome Cov.: 44

GnomAD4 genome Cov.: 26

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.76
BayesDel_addAF	Benign	-0.066	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.19	T;T
Eigen	Benign	-0.093
Eigen_PC	Benign	-0.25
FATHMM_MKL	Benign	0.61	D
LIST_S2	Benign	0.54	.;T
M_CAP	Uncertain	0.27	D
MetaRNN	Pathogenic	0.77	D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L;L
PrimateAI	Uncertain	0.76	T
PROVEAN	Uncertain	-3.3	.;D
REVEL	Benign	0.17
Sift	Uncertain	0.0050	.;D
Sift4G	Uncertain	0.013	D;D
Polyphen		1.0	D;D
Vest4		0.67
MutPred		0.50		Loss of helix (P = 0.0237);Loss of helix (P = 0.0237);
MVP		0.81
MPC		0.17
ClinPred		0.96	D
GERP RS		1.9
RBP_binding_hub_radar		1.0
RBP_regulation_power_radar		2.3
Varity_R		0.48
gMVP		0.45

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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

Other links and lift over

dbSNP: rs34877198; hg19: chr19-50435998;