rs3134615

Positions:

• chr1-39896394-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001033081.3(MYCL):​c.*978G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 203,210 control chromosomes in the GnomAD database, including 3,666 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 0.17 (2597 hom., cov: 32)
  • Exomes 𝑓: 0.19 (1069 hom.)
• Consequence: MYCL NM_001033081.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.184

Genes affected

MYCL (HGNC:7555): (MYCL proto-oncogene, bHLH transcription factor) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to act upstream of or within regulation of inner ear auditory receptor cell differentiation. Located in chromosome and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

MYCL-AS1 (HGNC:40386): (MYCL antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.232 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYCL	NM_001033081.3	c.*978G>T		3_prime_UTR_variant	2/2	ENST00000372816.3	NP_001028253.1
MYCL	NM_001033082.3	c.*978G>T		3_prime_UTR_variant	3/3		NP_001028254.2
MYCL-AS1	NR_183424.1	n.273-1349C>A		intron_variant
MYCL-AS1	NR_183425.1	n.36-1349C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYCL	ENST00000372816	c.*978G>T		3_prime_UTR_variant	2/2	2	NM_001033081.3	ENSP00000361903.2
MYCL	ENST00000397332	c.*978G>T		3_prime_UTR_variant	3/3	1		ENSP00000380494.2

Frequencies

GnomAD3 genomes AF: 0.173 AC: 26348 AN: 152070 Hom.: 2600 Cov.: 32

Gnomad AFR AF: 0.0901

Gnomad AMI AF: 0.0910

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.247

Gnomad EAS AF: 0.0374

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.180

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.235

Gnomad OTH AF: 0.163

GnomAD4 exome AF: 0.187 AC: 9557 AN: 51022 Hom.: 1069 Cov.: 0 AF XY: 0.192 AC XY: 4548 AN XY: 23724

Gnomad4 AFR exome AF: 0.0923

Gnomad4 AMR exome AF: 0.149

Gnomad4 ASJ exome AF: 0.271

Gnomad4 EAS exome AF: 0.0229

Gnomad4 SAS exome AF: 0.211

Gnomad4 FIN exome AF: 0.220

Gnomad4 NFE exome AF: 0.230

Gnomad4 OTH exome AF: 0.195

GnomAD4 genome AF: 0.173 AC: 26346 AN: 152188 Hom.: 2597 Cov.: 32 AF XY: 0.170 AC XY: 12682 AN XY: 74398

Gnomad4 AFR AF: 0.0900

Gnomad4 AMR AF: 0.143

Gnomad4 ASJ AF: 0.247

Gnomad4 EAS AF: 0.0375

Gnomad4 SAS AF: 0.217

Gnomad4 FIN AF: 0.180

Gnomad4 NFE AF: 0.235

Gnomad4 OTH AF: 0.161

Alfa AF: 0.222 Hom.: 4971

Bravo AF: 0.165

Asia WGS AF: 0.129 AC: 450 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	6.0
DANN	Benign	0.59

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3134615; hg19: chr1-40362066;