chr3-169780721-A-G

Position:

• chr3-169780721-A-G

Variant summary

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

The NM_018657.5(MYNN):​c.1192A>G​(p.Thr398Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000345 in 1,447,368 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: 0.0000035 (0 hom.)
• Consequence: MYNN NM_018657.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.32

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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYNN	NM_018657.5	c.1192A>G	p.Thr398Ala	missense_variant	4/8	ENST00000349841.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYNN	ENST00000349841.10	c.1192A>G	p.Thr398Ala	missense_variant	4/8	1	NM_018657.5	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000345 AC: 5 AN: 1447368 Hom.: 0 Cov.: 30 AF XY: 0.00000695 AC XY: 5 AN XY: 719614

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: 0.00000451

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

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

Jul 13, 2022

The c.1192A>G (p.T398A) alteration is located in exon 5 (coding exon 3) of the MYNN gene. This alteration results from a A to G substitution at nucleotide position 1192, causing the threonine (T) at amino acid position 398 to be replaced by an alanine (A). 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	0.89
BayesDel_addAF	Uncertain	0.062	T
BayesDel_noAF	Benign	-0.15
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.053	T;T;.
Eigen	Pathogenic	0.73
Eigen_PC	Pathogenic	0.76
FATHMM_MKL	Pathogenic	0.98	D
M_CAP	Benign	0.029	D
MetaRNN	Uncertain	0.54	D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L;L;L
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-1.8	N;N;N
REVEL	Uncertain	0.33
Sift	Uncertain	0.012	D;D;D
Sift4G	Benign	0.45	T;T;T
Polyphen		1.0	D;D;D
Vest4		0.63
MutPred		0.24		Gain of MoRF binding (P = 0.1836);Gain of MoRF binding (P = 0.1836);Gain of MoRF binding (P = 0.1836);
MVP		0.59
MPC		1.0
ClinPred		0.94	D
GERP RS		6.1
Varity_R		0.22
gMVP		0.58

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-169498509;