chr1-39897539-T-C

Variant names:

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

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.928A>G​(p.Thr310Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: MYCL NM_001033081.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.24
• 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: 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=0.12983036).

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.928A>G	p.Thr310Ala	missense	Exon 2 of 2	NP_001028253.1	P12524-1
	MYCL	NM_001033082.3		c.1018A>G	p.Thr340Ala	missense	Exon 3 of 3	NP_001028254.2	P12524-3
	MYCL-AS1	NR_183424.1		n.273-204T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYCL	ENST00000372816.3	TSL:2 MANE Select	c.928A>G	p.Thr310Ala	missense	Exon 2 of 2	ENSP00000361903.2	P12524-1
	MYCL	ENST00000397332.3	TSL:1	c.1018A>G	p.Thr340Ala	missense	Exon 3 of 3	ENSP00000380494.2	P12524-3
	MYCL-AS1	ENST00000837554.1		n.207T>C		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461888 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727244

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112010

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000302

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	0.052
BayesDel_addAF	Benign	-0.010	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	18
DANN	Benign	0.83
DEOGEN2	Uncertain	0.53	D
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.20
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.050	D
MetaRNN	Benign	0.13	T
MetaSVM	Uncertain	0.0021	D
MutationAssessor	Benign	0.31	N
PhyloP100		2.2
PrimateAI	Benign	0.46	T
PROVEAN	Benign	0.36	N
REVEL	Benign	0.25
Sift	Benign	1.0	T
Sift4G	Benign	0.63	T
Polyphen		0.0030	B
Vest4		0.052
MutPred		0.45		Loss of glycosylation at T310 (P = 0.058)
MVP		0.51
MPC		0.66
ClinPred		0.099	T
GERP RS		3.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.051
gMVP		0.25
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: rs1177671093; hg19: chr1-40363211;