NM_018657.5:c.18C>G

Variant names:

• chr3-169774313-C-G
• rs10936599
• NM_018657.5:c.18C>G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_018657.5(MYNN):​c.18C>G​(p.His6Gln) 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 pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Synonymous variant affecting the same amino acid position (i.e. H6H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MYNN NM_018657.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.15
• Publications: 323 publications found

Genes affected

MYNN (HGNC:14955): (myoneurin) This gene encodes a member of the BTB/POZ and zinc finger domain-containing protein family that are involved in the control of gene expression. Alternative splicing results in multiple transcript variants and a pseudogene has been identified on chromosome 14. [provided by RefSeq, Jun 2010]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.827

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018657.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYNN	NM_018657.5	MANE Select	c.18C>G	p.His6Gln	missense	Exon 2 of 8	NP_061127.1
	MYNN	NM_001185118.2		c.18C>G	p.His6Gln	missense	Exon 3 of 9	NP_001172047.1
	MYNN	NM_001185119.1		c.18C>G	p.His6Gln	missense	Exon 1 of 6	NP_001172048.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYNN	ENST00000349841.10	TSL:1 MANE Select	c.18C>G	p.His6Gln	missense	Exon 2 of 8	ENSP00000326240.4
	MYNN	ENST00000356716.8	TSL:1	c.18C>G	p.His6Gln	missense	Exon 3 of 9	ENSP00000349150.3
	MYNN	ENST00000544106.5	TSL:1	c.18C>G	p.His6Gln	missense	Exon 1 of 6	ENSP00000440637.1

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	Uncertain	0.45
BayesDel_addAF	Pathogenic	0.34	D
BayesDel_noAF	Pathogenic	0.25
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.17	T
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.88	D
M_CAP	Uncertain	0.098	D
MetaRNN	Pathogenic	0.83	D
MetaSVM	Uncertain	0.28	D
MutationAssessor	Uncertain	2.9	M
PhyloP100		3.2
PrimateAI	Uncertain	0.74	T
PROVEAN	Uncertain	-2.7	D
REVEL	Pathogenic	0.68
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.079	T
Polyphen		1.0	D
Vest4		0.89
MutPred		0.43		Loss of catalytic residue at E8 (P = 0.148)
MVP		0.90
MPC		1.1
ClinPred		0.99	D
GERP RS		3.9
PromoterAI		0.011	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.94
gMVP		0.88
Mutation Taster		=16/84	disease causing

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: rs10936599; hg19: chr3-169492101;