3-169774444-G-A

Position:

• chr3-169774444-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_018657.5(MYNN):​c.149G>A​(p.Gly50Asp) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,828 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: MYNN NM_018657.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.89

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]

MYNN (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYNN	NM_018657.5	c.149G>A	p.Gly50Asp	missense_variant	2/8	ENST00000349841.10	NP_061127.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYNN	ENST00000349841.10	c.149G>A	p.Gly50Asp	missense_variant	2/8	1	NM_018657.5	ENSP00000326240.4
MYNN	ENST00000356716.8	c.149G>A	p.Gly50Asp	missense_variant	3/9	1		ENSP00000349150.3
MYNN	ENST00000544106.5	c.149G>A	p.Gly50Asp	missense_variant	1/6	1		ENSP00000440637.1
MYNN	ENST00000602751.5	n.149G>A		non_coding_transcript_exon_variant	2/8	1		ENSP00000473654.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461828 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727206

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 21, 2023

The c.149G>A (p.G50D) alteration is located in exon 3 (coding exon 1) of the MYNN gene. This alteration results from a G to A substitution at nucleotide position 149, causing the glycine (G) at amino acid position 50 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.81
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.18
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T;T;.
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.85	.;D;D
M_CAP	Benign	0.036	D
MetaRNN	Uncertain	0.70	D;D;D
MetaSVM	Uncertain	-0.18	T
MutationAssessor	Benign	-0.63	N;N;N
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-0.82	N;N;N
REVEL	Uncertain	0.40
Sift	Uncertain	0.028	D;D;D
Sift4G	Benign	0.069	T;T;T
Polyphen		1.0	D;D;D
Vest4		0.64
MutPred		0.44		Loss of loop (P = 0.0374);Loss of loop (P = 0.0374);Loss of loop (P = 0.0374);
MVP		0.82
MPC		1.2
ClinPred		0.91	D
GERP RS		5.7
Varity_R		0.63
gMVP		0.79

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: rs758173459; hg19: chr3-169492232;