rs3134614

Positions:

• chr1-39897382-G-C

Variant summary

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

The NM_001033081.3(MYCL):​c.1085C>G​(p.Thr362Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.881 in 1,597,414 control chromosomes in the GnomAD database, including 620,979 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.91 (63209 hom., cov: 33)
  • Exomes 𝑓: 0.88 (557770 hom.)
• Consequence: MYCL NM_001033081.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.28

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=5.394342E-7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYCL	NM_001033081.3	c.1085C>G	p.Thr362Ser	missense_variant	2/2	ENST00000372816.3
MYCL-AS1	NR_183424.1	n.273-361G>C		intron_variant, non_coding_transcript_variant
MYCL	NM_001033082.3	c.1175C>G	p.Thr392Ser	missense_variant	3/3
MYCL-AS1	NR_183425.1	n.36-361G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYCL	ENST00000372816.3	c.1085C>G	p.Thr362Ser	missense_variant	2/2	2	NM_001033081.3	P4
MYCL	ENST00000397332.3	c.1175C>G	p.Thr392Ser	missense_variant	3/3	1		A1

Frequencies

GnomAD3 genomes AF: 0.909 AC: 138378 AN: 152194 Hom.: 63149 Cov.: 33

Gnomad AFR AF: 0.977

Gnomad AMI AF: 0.845

Gnomad AMR AF: 0.897

Gnomad ASJ AF: 0.853

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.832

Gnomad FIN AF: 0.895

Gnomad MID AF: 0.892

Gnomad NFE AF: 0.875

Gnomad OTH AF: 0.905

GnomAD3 exomes AF: 0.885 AC: 217303 AN: 245514 Hom.: 96484 AF XY: 0.879 AC XY: 116669 AN XY: 132662

Gnomad AFR exome AF: 0.977

Gnomad AMR exome AF: 0.872

Gnomad ASJ exome AF: 0.856

Gnomad EAS exome AF: 0.999

Gnomad SAS exome AF: 0.826

Gnomad FIN exome AF: 0.894

Gnomad NFE exome AF: 0.873

Gnomad OTH exome AF: 0.885

GnomAD4 exome AF: 0.878 AC: 1268532 AN: 1445102 Hom.: 557770 Cov.: 47 AF XY: 0.875 AC XY: 626814 AN XY: 716116

Gnomad4 AFR exome AF: 0.980

Gnomad4 AMR exome AF: 0.876

Gnomad4 ASJ exome AF: 0.860

Gnomad4 EAS exome AF: 0.999

Gnomad4 SAS exome AF: 0.822

Gnomad4 FIN exome AF: 0.885

Gnomad4 NFE exome AF: 0.874

Gnomad4 OTH exome AF: 0.885

GnomAD4 genome AF: 0.909 AC: 138499 AN: 152312 Hom.: 63209 Cov.: 33 AF XY: 0.910 AC XY: 67746 AN XY: 74474

Gnomad4 AFR AF: 0.977

Gnomad4 AMR AF: 0.897

Gnomad4 ASJ AF: 0.853

Gnomad4 EAS AF: 0.998

Gnomad4 SAS AF: 0.831

Gnomad4 FIN AF: 0.895

Gnomad4 NFE AF: 0.875

Gnomad4 OTH AF: 0.906

Alfa AF: 0.886 Hom.: 16783

Bravo AF: 0.914

TwinsUK AF: 0.872 AC: 3234

ALSPAC AF: 0.880 AC: 3392

ESP6500AA AF: 0.975 AC: 4295

ESP6500EA AF: 0.867 AC: 7458

ExAC AF: 0.884 AC: 107296

Asia WGS AF: 0.939 AC: 3267 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	18
DANN	Benign	0.82
DEOGEN2	Benign	0.23	.;T
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.19	T;T
MetaRNN	Benign	5.4e-7	T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-0.77	.;N
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.40	T
PROVEAN	Benign	0.17	N;N
REVEL	Benign	0.21
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0	.;B
Vest4		0.019
MutPred		0.16		.;Gain of disorder (P = 0.1617);
MPC		0.60
ClinPred		0.0012	T
GERP RS		4.5
Varity_R		0.048
gMVP		0.086

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

Publications

LitVar

Other links and lift over

dbSNP: rs3134614; hg19: chr1-40363054; COSMIC: COSV65693710; COSMIC: COSV65693710;