rs1268967437

Variant names:

• chr1-39901089-C-A
• rs1268967437
• NM_001033081.3:c.346G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001033081.3(MYCL):​c.346G>T​(p.Gly116Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000444 in 1,577,922 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: MYCL NM_001033081.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.13
• Publications: 1 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21521878).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYCL	NM_001033081.3	MANE Select	c.346G>T	p.Gly116Cys	missense	Exon 1 of 2	NP_001028253.1	P12524-1
	MYCL	NM_001033082.3		c.436G>T	p.Gly146Cys	missense	Exon 2 of 3	NP_001028254.2	P12524-3
	MYCL	NM_005376.5		c.436G>T	p.Gly146Cys	missense	Exon 2 of 2	NP_005367.2	P12524-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYCL	ENST00000372816.3	TSL:2 MANE Select	c.346G>T	p.Gly116Cys	missense	Exon 1 of 2	ENSP00000361903.2	P12524-1
	MYCL	ENST00000397332.3	TSL:1	c.436G>T	p.Gly146Cys	missense	Exon 2 of 3	ENSP00000380494.2	P12524-3
	MYCL	ENST00000372815.1	TSL:1	c.436G>T	p.Gly146Cys	missense	Exon 2 of 2	ENSP00000361902.1	P12524-2

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152192 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000531 AC: 1 AN: 188306 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000126

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000281 AC: 4 AN: 1425730 Hom.: 0 Cov.: 32 AF XY: 0.00000283 AC XY: 2 AN XY: 706028

African (AFR) AF: 0.00 AC: 0 AN: 32716

American (AMR) AF: 0.00 AC: 0 AN: 38852

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25252

East Asian (EAS) AF: 0.00 AC: 0 AN: 37944

South Asian (SAS) AF: 0.00 AC: 0 AN: 82206

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49804

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5650

European-Non Finnish (NFE) AF: 0.00000366 AC: 4 AN: 1094348

Other (OTH) AF: 0.00 AC: 0 AN: 58958

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152192 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74352

African (AFR) AF: 0.00 AC: 0 AN: 41460

American (AMR) AF: 0.00 AC: 0 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10632

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68010

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	T
Eigen	Benign	0.14
Eigen_PC	Benign	0.079
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L
PhyloP100		2.1
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.093
Sift	Uncertain	0.012	D
Sift4G	Uncertain	0.054	T
Polyphen		0.97	D
Vest4		0.35
MutPred		0.45		Gain of catalytic residue at P115 (P = 0.0073)
MVP		0.12
MPC		1.7
ClinPred		0.46	T
GERP RS		3.2
Varity_R		0.21
gMVP		0.29
Mutation Taster		=86/14	polymorphism

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: rs1268967437; hg19: chr1-40366761;