chr3-169774313-C-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. 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;