1-39897923-C-T

Variant names:

• chr1-39897923-C-T
• rs1003519625
• NM_001033081.3:c.544G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001033081.3(MYCL):​c.544G>A​(p.Gly182Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. G182C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MYCL NM_001033081.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.86
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.028412402).

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.544G>A	p.Gly182Ser	missense	Exon 2 of 2	NP_001028253.1	P12524-1
	MYCL	NM_001033082.3		c.634G>A	p.Gly212Ser	missense	Exon 3 of 3	NP_001028254.2	P12524-3
	MYCL-AS1	NR_183424.1		n.453C>T		non_coding_transcript_exon	Exon 2 of 3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYCL	ENST00000372816.3	TSL:2 MANE Select	c.544G>A	p.Gly182Ser	missense	Exon 2 of 2	ENSP00000361903.2	P12524-1
	MYCL	ENST00000397332.3	TSL:1	c.634G>A	p.Gly212Ser	missense	Exon 3 of 3	ENSP00000380494.2	P12524-3
	MYCL-AS1	ENST00000418255.2	TSL:2	n.506C>T		non_coding_transcript_exon	Exon 2 of 3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	11
DANN	Benign	0.90
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.31	T
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.028	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.11	N
PhyloP100		1.9
PrimateAI	Benign	0.31	T
PROVEAN	Benign	1.0	N
REVEL	Benign	0.075
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0020	B
Vest4		0.043
MutPred		0.28		Gain of disorder (P = 0.0374)
MVP		0.014
MPC		0.68
ClinPred		0.17	T
GERP RS		4.0
Varity_R		0.077
gMVP		0.15
Mutation Taster		=94/6	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: rs1003519625; hg19: chr1-40363595;