19-49932611-C-G

Variant names:

• chr19-49932611-C-G
• NM_001193646.2:c.368C>G

Variant summary

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

The NM_001193646.2(ATF5):​c.368C>G​(p.Pro123Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 19)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ATF5 NM_001193646.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.55
• 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.

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.368C>G	p.Pro123Arg	missense	Exon 3 of 3	NP_001180575.1	Q9Y2D1
	ATF5	NM_001290746.2		c.368C>G	p.Pro123Arg	missense	Exon 3 of 3	NP_001277675.1	Q9Y2D1
	ATF5	NM_012068.6		c.368C>G	p.Pro123Arg	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.368C>G	p.Pro123Arg	missense	Exon 3 of 3	ENSP00000396954.1	Q9Y2D1
	ENSG00000269179	ENST00000451973.1	TSL:2	n.*77+19280G>C		intron	N/A	ENSP00000391489.1	H7BZU6
	ATF5	ENST00000595125.5	TSL:2	c.368C>G	p.Pro123Arg	missense	Exon 4 of 4	ENSP00000470633.1	Q9Y2D1

Frequencies

GnomAD3 genomes Cov.: 19

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1404828 Hom.: 0 Cov.: 44 AF XY: 0.00 AC XY: 0 AN XY: 693982

African (AFR) AF: 0.00 AC: 0 AN: 32542

American (AMR) AF: 0.00 AC: 0 AN: 38610

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24772

East Asian (EAS) AF: 0.00 AC: 0 AN: 37202

South Asian (SAS) AF: 0.00 AC: 0 AN: 80002

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48966

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4110

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1080566

Other (OTH) AF: 0.00 AC: 0 AN: 58058

GnomAD4 genome Cov.: 19

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.052	T
Eigen	Benign	-0.059
Eigen_PC	Benign	-0.070
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.46	T
M_CAP	Uncertain	0.23	D
MetaRNN	Uncertain	0.63	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L
PhyloP100		2.5
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.12
Sift	Benign	0.044	D
Sift4G	Uncertain	0.0090	D
Polyphen		0.84	P
Vest4		0.29
MutPred		0.48		Loss of glycosylation at P123 (P = 0.0048)
MVP		0.64
MPC		0.063
ClinPred		0.47	T
GERP RS		3.7
Varity_R		0.040
gMVP		0.38
Mutation Taster		=79/21	polymorphism

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

Other links and lift over

hg19: chr19-50435868;