rs3134614

Variant names:

• chr1-39897382-G-C
• rs3134614
• NM_001033081.3:c.1085C>G

Your query was ambiguous. Multiple possible variants found:

• chr1-39897382-G-C
• chr1-39897382-G-T

Variant summary

Our verdict is Benign. The variant received -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. 16/22 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 the same amino acid substitution has been previously reported as Likely benign in 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:40386): (MYCL antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
MYCL	NM_001033081.3	c.1085C>G	p.Thr362Ser	missense_variant	Exon 2 of 2	ENST00000372816.3	NP_001028253.1
MYCL	NM_001033082.3	c.1175C>G	p.Thr392Ser	missense_variant	Exon 3 of 3		NP_001028254.2
MYCL-AS1	NR_183424.1	n.273-361G>C		intron_variant	Intron 1 of 2
MYCL-AS1	NR_183425.1	n.36-361G>C		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYCL	ENST00000372816.3	c.1085C>G	p.Thr362Ser	missense_variant	Exon 2 of 2	2	NM_001033081.3	ENSP00000361903.2
MYCL	ENST00000397332.3	c.1175C>G	p.Thr392Ser	missense_variant	Exon 3 of 3	1		ENSP00000380494.2

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

GnomAD2 exomes AF: 0.885 AC: 217303 AN: 245514 AF XY: 0.879

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 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 AC: 32367 AN: 33022

Gnomad4 AMR exome AF: 0.876 AC: 38233 AN: 43648

Gnomad4 ASJ exome AF: 0.860 AC: 21863 AN: 25422

Gnomad4 EAS exome AF: 0.999 AC: 39302 AN: 39340

Gnomad4 SAS exome AF: 0.822 AC: 69935 AN: 85028

Gnomad4 FIN exome AF: 0.885 AC: 46947 AN: 53020

Gnomad4 NFE exome AF: 0.874 AC: 962204 AN: 1100382

Gnomad4 Remaining exome AF: 0.885 AC: 52697 AN: 59534

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 AC: 0.97715 AN: 0.97715

Gnomad4 AMR AF: 0.897 AC: 0.897491 AN: 0.897491

Gnomad4 ASJ AF: 0.853 AC: 0.852823 AN: 0.852823

Gnomad4 EAS AF: 0.998 AC: 0.998456 AN: 0.998456

Gnomad4 SAS AF: 0.831 AC: 0.831468 AN: 0.831468

Gnomad4 FIN AF: 0.895 AC: 0.894533 AN: 0.894533

Gnomad4 NFE AF: 0.875 AC: 0.875463 AN: 0.875463

Gnomad4 OTH AF: 0.906 AC: 0.906427 AN: 0.906427

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
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
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

Publications

LitVar

Other links and lift over

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