3-169778908-T-C

Position:

• chr3-169778908-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000349841.10(MYNN):​c.407T>C​(p.Ile136Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,742 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: MYNN ENST00000349841.10 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.67

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]

(HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16911054).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYNN	NM_018657.5	c.407T>C	p.Ile136Thr	missense_variant	3/8	ENST00000349841.10	NP_061127.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYNN	ENST00000349841.10	c.407T>C	p.Ile136Thr	missense_variant	3/8	1	NM_018657.5	ENSP00000326240	P1
	ENST00000602342.1	n.1427A>G		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461742 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727168

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

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

Jun 17, 2024

The c.407T>C (p.I136T) alteration is located in exon 4 (coding exon 2) of the MYNN gene. This alteration results from a T to C substitution at nucleotide position 407, causing the isoleucine (I) at amino acid position 136 to be replaced by a threonine (T). 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	Benign	0.19
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.012	T;T;.
Eigen	Benign	0.083
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.90	.;D;D
M_CAP	Benign	0.0061	T
MetaRNN	Benign	0.17	T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.0	L;L;L
MutationTaster	Benign	0.96	D;D;D;D
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.61	N;N;N
REVEL	Benign	0.14
Sift	Benign	0.22	T;T;T
Sift4G	Benign	0.21	T;T;T
Polyphen		0.041	B;B;P
Vest4		0.49
MutPred		0.54		Gain of disorder (P = 0.0183);Gain of disorder (P = 0.0183);Gain of disorder (P = 0.0183);
MVP		0.16
MPC		0.44
ClinPred		0.54	D
GERP RS		5.3
Varity_R		0.089
gMVP		0.40

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1778429247; hg19: chr3-169496696;