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. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 43 publications found

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001033081.3. 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
	MYCL	NM_001033081.3	MANE Select	c.1085C>G	p.Thr362Ser	missense	Exon 2 of 2	NP_001028253.1
	MYCL	NM_001033082.3		c.1175C>G	p.Thr392Ser	missense	Exon 3 of 3	NP_001028254.2
	MYCL-AS1	NR_183424.1		n.273-361G>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYCL	ENST00000372816.3	TSL:2 MANE Select	c.1085C>G	p.Thr362Ser	missense	Exon 2 of 2	ENSP00000361903.2
	MYCL	ENST00000397332.3	TSL:1	c.1175C>G	p.Thr392Ser	missense	Exon 3 of 3	ENSP00000380494.2
	MYCL-AS1	ENST00000837552.1		n.50G>C		non_coding_transcript_exon	Exon 1 of 3

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

African (AFR) AF: 0.980 AC: 32367 AN: 33022

American (AMR) AF: 0.876 AC: 38233 AN: 43648

Ashkenazi Jewish (ASJ) AF: 0.860 AC: 21863 AN: 25422

East Asian (EAS) AF: 0.999 AC: 39302 AN: 39340

South Asian (SAS) AF: 0.822 AC: 69935 AN: 85028

European-Finnish (FIN) AF: 0.885 AC: 46947 AN: 53020

Middle Eastern (MID) AF: 0.873 AC: 4984 AN: 5706

European-Non Finnish (NFE) AF: 0.874 AC: 962204 AN: 1100382

Other (OTH) 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

African (AFR) AF: 0.977 AC: 40626 AN: 41576

American (AMR) AF: 0.897 AC: 13737 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.853 AC: 2961 AN: 3472

East Asian (EAS) AF: 0.998 AC: 5174 AN: 5182

South Asian (SAS) AF: 0.831 AC: 4011 AN: 4824

European-Finnish (FIN) AF: 0.895 AC: 9491 AN: 10610

Middle Eastern (MID) AF: 0.888 AC: 261 AN: 294

European-Non Finnish (NFE) AF: 0.875 AC: 59549 AN: 68020

Other (OTH) AF: 0.906 AC: 1918 AN: 2116

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 v4.9

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
MetaRNN	Benign	5.4e-7	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-0.77	N
PhyloP100		2.3
PrimateAI	Benign	0.40	T
PROVEAN	Benign	0.17	N
REVEL	Benign	0.21
Sift	Benign	1.0	T
Sift4G	Benign	1.0	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

Other links and lift over

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