1-39900984-G-A

Variant names:

• chr1-39900984-G-A
• rs760897624
• NM_001033081.3:c.451C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001033081.3(MYCL):​c.451C>T​(p.Pro151Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000824 in 1,335,702 control chromosomes in the GnomAD database, including 1 homozygotes. 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P151H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000082 (1 hom.)
• Consequence: MYCL NM_001033081.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.13
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.072830945).

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.451C>T	p.Pro151Ser	missense	Exon 1 of 2	NP_001028253.1	P12524-1
	MYCL	NM_001033082.3		c.541C>T	p.Pro181Ser	missense	Exon 2 of 3	NP_001028254.2	P12524-3
	MYCL	NM_005376.5		c.541C>T	p.Pro181Ser	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.451C>T	p.Pro151Ser	missense	Exon 1 of 2	ENSP00000361903.2	P12524-1
	MYCL	ENST00000397332.3	TSL:1	c.541C>T	p.Pro181Ser	missense	Exon 2 of 3	ENSP00000380494.2	P12524-3
	MYCL	ENST00000372815.1	TSL:1	c.541C>T	p.Pro181Ser	missense	Exon 2 of 2	ENSP00000361902.1	P12524-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000411 AC: 4 AN: 97268 AF XY: 0.0000392

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000465

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000824 AC: 11 AN: 1335702 Hom.: 1 Cov.: 33 AF XY: 0.0000122 AC XY: 8 AN XY: 653868

African (AFR) AF: 0.00 AC: 0 AN: 28778

American (AMR) AF: 0.00 AC: 0 AN: 23828

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20528

East Asian (EAS) AF: 0.000314 AC: 11 AN: 35058

South Asian (SAS) AF: 0.00 AC: 0 AN: 69518

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46152

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4932

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1051936

Other (OTH) AF: 0.00 AC: 0 AN: 54972

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

ExAC AF: 0.0000291 AC: 3

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	0.082
BayesDel_addAF	Benign	-0.025	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T
Eigen	Benign	0.12
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Benign	0.55	D
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.057	D
MetaRNN	Benign	0.073	T
MetaSVM	Benign	-0.69	T
MutationAssessor	Benign	0.66	N
PhyloP100		3.1
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-0.30	N
REVEL	Benign	0.12
Sift	Benign	0.43	T
Sift4G	Benign	0.46	T
Polyphen		0.92	P
Vest4		0.24
MutPred		0.15		Gain of phosphorylation at P151 (P = 0.0322)
MVP		0.47
MPC		0.79
ClinPred		0.15	T
GERP RS		5.0
Varity_R		0.10
gMVP		0.18
Mutation Taster		=92/8	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: rs760897624; hg19: chr1-40366656;