19-49930969-A-C

Variant names:

• chr19-49930969-A-C
• rs1256104542
• NM_001193646.2:c.119A>C

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.119A>C​(p.Tyr40Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000881 in 1,589,002 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000084 (0 hom.)
• Consequence: ATF5 NM_001193646.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.944
• Publications: 1 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=0.25653958).

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.119A>C	p.Tyr40Ser	missense	Exon 2 of 3	NP_001180575.1	Q9Y2D1
	ATF5	NM_001290746.2		c.119A>C	p.Tyr40Ser	missense	Exon 2 of 3	NP_001277675.1	Q9Y2D1
	ATF5	NM_012068.6		c.119A>C	p.Tyr40Ser	missense	Exon 3 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.119A>C	p.Tyr40Ser	missense	Exon 2 of 3	ENSP00000396954.1	Q9Y2D1
	ENSG00000269179	ENST00000451973.1	TSL:2	n.*77+20922T>G		intron	N/A	ENSP00000391489.1	H7BZU6
	ATF5	ENST00000595125.5	TSL:2	c.119A>C	p.Tyr40Ser	missense	Exon 3 of 4	ENSP00000470633.1	Q9Y2D1

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152104 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000835 AC: 12 AN: 1436898 Hom.: 0 Cov.: 31 AF XY: 0.00000982 AC XY: 7 AN XY: 712514

African (AFR) AF: 0.0000301 AC: 1 AN: 33170

American (AMR) AF: 0.00 AC: 0 AN: 39758

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25450

East Asian (EAS) AF: 0.00 AC: 0 AN: 38804

South Asian (SAS) AF: 0.00 AC: 0 AN: 82432

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51646

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5508

European-Non Finnish (NFE) AF: 0.00000999 AC: 11 AN: 1100676

Other (OTH) AF: 0.00 AC: 0 AN: 59454

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152104 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74312

African (AFR) AF: 0.00 AC: 0 AN: 41436

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10592

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 67972

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000227

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	-0.058	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	16
DANN	Benign	0.93
DEOGEN2	Benign	0.039	T
Eigen	Benign	-0.083
Eigen_PC	Benign	-0.098
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.025	D
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.20	N
PhyloP100		0.94
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-0.47	N
REVEL	Benign	0.15
Sift	Uncertain	0.0040	D
Sift4G	Benign	0.39	T
Polyphen		0.91	P
Vest4		0.45
MutPred		0.40		Gain of disorder (P = 0.0023)
MVP		0.67
MPC		0.028
ClinPred		0.20	T
GERP RS		3.6
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.9
Varity_R		0.091
gMVP		0.44
Mutation Taster		=83/17	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

dbSNP: rs1256104542; hg19: chr19-50434226;