1-39897539-T-G

Variant names:

• chr1-39897539-T-G
• rs1177671093
• NM_001033081.3:c.928A>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001033081.3(MYCL):​c.928A>C​(p.Thr310Pro) 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. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T310A) 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: 2.24

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28439057).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYCL	NM_001033081.3	c.928A>C	p.Thr310Pro	missense_variant	Exon 2 of 2	ENST00000372816.3	NP_001028253.1
MYCL	NM_001033082.3	c.1018A>C	p.Thr340Pro	missense_variant	Exon 3 of 3		NP_001028254.2
MYCL-AS1	NR_183424.1	n.273-204T>G		intron_variant	Intron 1 of 2
MYCL-AS1	NR_183425.1	n.36-204T>G		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYCL	ENST00000372816.3	c.928A>C	p.Thr310Pro	missense_variant	Exon 2 of 2	2	NM_001033081.3	ENSP00000361903.2
MYCL	ENST00000397332.3	c.1018A>C	p.Thr340Pro	missense_variant	Exon 3 of 3	1		ENSP00000380494.2
MYCL-AS1	ENST00000418255.1	n.-206T>G		upstream_gene_variant		2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Pathogenic	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Benign	22
DANN	Benign	0.95
DEOGEN2	Uncertain	0.75	.;D
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.10
FATHMM_MKL	Benign	0.56	D
LIST_S2	Benign	0.60	T;T
M_CAP	Benign	0.073	D
MetaRNN	Benign	0.28	T;T
MetaSVM	Uncertain	0.19	D
MutationAssessor	Benign	1.3	.;L
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-1.1	N;N
REVEL	Uncertain	0.43
Sift	Benign	0.26	T;T
Sift4G	Benign	0.24	T;T
Polyphen		0.0070	.;B
Vest4		0.26
MutPred		0.52		.;Gain of catalytic residue at P309 (P = 0.0164);
MVP		0.60
MPC		0.89
ClinPred		0.27	T
GERP RS		3.4
Varity_R		0.18
gMVP		0.58

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: rs1177671093; hg19: chr1-40363211;