19-49933723-G-C

Variant names:

• chr19-49933723-G-C
• rs8647
• NM_001193646.2:c.*631G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001193646.2(ATF5):​c.*631G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 30)
• Consequence: ATF5 NM_001193646.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.290
• Publications: 14 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATF5	NM_001193646.2	MANE Select	c.*631G>C		3_prime_UTR	Exon 3 of 3	NP_001180575.1
	ATF5	NM_001290746.2		c.*631G>C		3_prime_UTR	Exon 3 of 3	NP_001277675.1
	ATF5	NM_012068.6		c.*631G>C		3_prime_UTR	Exon 4 of 4	NP_036200.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATF5	ENST00000423777.7	TSL:1 MANE Select	c.*631G>C		3_prime_UTR	Exon 3 of 3	ENSP00000396954.1
	ENSG00000269179	ENST00000451973.1	TSL:2	n.*77+18168C>G		intron	N/A	ENSP00000391489.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.12
DANN	Benign	0.45
PhyloP100		-0.29
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3

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: rs8647; hg19: chr19-50436980;