rs10936599

chr3-169774313-C-Gchr3-169774313-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 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

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

Verdict is Uncertain_significance. Variant got 3 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYNN	NM_018657.5	c.18C>G	p.His6Gln	missense_variant	2/8	ENST00000349841.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYNN	ENST00000349841.10	c.18C>G	p.His6Gln	missense_variant	2/8	1	NM_018657.5	P1
MYNN	ENST00000356716.8	c.18C>G	p.His6Gln	missense_variant	3/9	1		P1
MYNN	ENST00000544106.5	c.18C>G	p.His6Gln	missense_variant	1/6	1
MYNN	ENST00000602751.5	c.18C>G	p.His6Gln	missense_variant, NMD_transcript_variant	2/8	1

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	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;T;.
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Uncertain	0.92	D
M_CAP	Uncertain	0.098	D
MetaRNN	Pathogenic	0.83	D;D;D
MetaSVM	Uncertain	0.28	D
MutationAssessor	Uncertain	2.9	M;M;M
MutationTaster	Benign	0.000068	P;P;P;P
PrimateAI	Uncertain	0.74	T
PROVEAN	Uncertain	-2.7	D;D;N
REVEL	Pathogenic	0.68
Sift	Pathogenic	0.0	D;D;D
Sift4G	Benign	0.079	T;T;T
Polyphen		1.0	D;D;D
Vest4		0.89
MutPred		0.43		Loss of catalytic residue at E8 (P = 0.148);Loss of catalytic residue at E8 (P = 0.148);Loss of catalytic residue at E8 (P = 0.148);
MVP		0.90
MPC		1.1
ClinPred		0.99	D
GERP RS		3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.94
gMVP		0.88

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: rs10936599; hg19: chr3-169492101;