NM_003920.5:c.-61-1077A>G

Variant names:

• chr12-56435308-T-C
• rs7302060
• NM_003920.5:c.-61-1077A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003920.5(TIMELESS):​c.-61-1077A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.342 in 151,484 control chromosomes in the GnomAD database, including 10,578 homozygotes. 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: 𝑓 0.34 (10578 hom., cov: 30)
• Consequence: TIMELESS NM_003920.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.94
• Publications: 18 publications found

Genes affected

TIMELESS (HGNC:11813): (timeless circadian regulator) The protein encoded by this gene is highly conserved and is involved in cell survival after damage or stress, increase in DNA polymerase epsilon activity, maintenance of telomere length, and epithelial cell morphogenesis. The encoded protein also plays a role in the circadian rhythm autoregulatory loop, interacting with the PERIOD genes (PER1, PER2, and PER3) and others to downregulate activation of PER1 by CLOCK/ARNTL. Changes in this gene or its expression may promote prostate cancer, lung cancer, breast cancer, and mental disorders. [provided by RefSeq, Feb 2014]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.627 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003920.5. 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
	TIMELESS	NM_003920.5	MANE Select	c.-61-1077A>G		intron	N/A	NP_003911.2
	TIMELESS	NM_001330295.2		c.-61-1077A>G		intron	N/A	NP_001317224.1
	TIMELESS	NR_138471.2		n.118-1077A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TIMELESS	ENST00000553532.6	TSL:1 MANE Select	c.-61-1077A>G		intron	N/A	ENSP00000450607.1
	TIMELESS	ENST00000229201.4	TSL:5	c.-61-1077A>G		intron	N/A	ENSP00000229201.4

Frequencies

GnomAD3 genomes AF: 0.342 AC: 51832 AN: 151370 Hom.: 10577 Cov.: 30

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.316

Gnomad AMR AF: 0.454

Gnomad ASJ AF: 0.472

Gnomad EAS AF: 0.646

Gnomad SAS AF: 0.382

Gnomad FIN AF: 0.352

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.410

Gnomad OTH AF: 0.411

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.342 AC: 51830 AN: 151484 Hom.: 10578 Cov.: 30 AF XY: 0.343 AC XY: 25359 AN XY: 73996

African (AFR) AF: 0.129 AC: 5337 AN: 41274

American (AMR) AF: 0.454 AC: 6908 AN: 15200

Ashkenazi Jewish (ASJ) AF: 0.472 AC: 1636 AN: 3466

East Asian (EAS) AF: 0.645 AC: 3307 AN: 5124

South Asian (SAS) AF: 0.382 AC: 1828 AN: 4780

European-Finnish (FIN) AF: 0.352 AC: 3688 AN: 10464

Middle Eastern (MID) AF: 0.446 AC: 131 AN: 294

European-Non Finnish (NFE) AF: 0.410 AC: 27854 AN: 67872

Other (OTH) AF: 0.406 AC: 854 AN: 2102

Alfa AF: 0.391 Hom.: 33887

Bravo AF: 0.350

Asia WGS AF: 0.435 AC: 1513 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.0070
DANN	Benign	0.47
PhyloP100		-2.9
Mutation Taster		=100/0	polymorphism (auto)

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: rs7302060; hg19: chr12-56829092;