17-39729584-C-A

Variant summary

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

The NM_032339.5(MIEN1):c.286G>T(p.Ala96Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MIEN1 NM_032339.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.73

Genes affected

MIEN1 (HGNC:28230): (migration and invasion enhancer 1) Involved in negative regulation of apoptotic process; positive regulation of cell migration; and positive regulation of filopodium assembly. Located in several cellular components, including centriolar satellite; cytosol; and nucleoplasm. Is intrinsic component of the cytoplasmic side of the plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ERBB2 (HGNC:3430): (erb-b2 receptor tyrosine kinase 2) This gene encodes a member of the epidermal growth factor (EGF) receptor family of receptor tyrosine kinases. This protein has no ligand binding domain of its own and therefore cannot bind growth factors. However, it does bind tightly to other ligand-bound EGF receptor family members to form a heterodimer, stabilizing ligand binding and enhancing kinase-mediated activation of downstream signalling pathways, such as those involving mitogen-activated protein kinase and phosphatidylinositol-3 kinase. Allelic variations at amino acid positions 654 and 655 of isoform a (positions 624 and 625 of isoform b) have been reported, with the most common allele, Ile654/Ile655, shown here. Amplification and/or overexpression of this gene has been reported in numerous cancers, including breast and ovarian tumors. Alternative splicing results in several additional transcript variants, some encoding different isoforms and others that have not been fully characterized. [provided by RefSeq, Jul 2008]

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
MIEN1	NM_032339.5	c.286G>T	p.Ala96Ser	missense_variant	4/4	ENST00000394231.8
MIEN1	NM_001330206.2	c.*14G>T		3_prime_UTR_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MIEN1	ENST00000394231.8	c.286G>T	p.Ala96Ser	missense_variant	4/4	1	NM_032339.5	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Jun 26, 2023

The c.286G>T (p.A96S) alteration is located in exon 4 (coding exon 4) of the MIEN1 gene. This alteration results from a G to T substitution at nucleotide position 286, causing the alanine (A) at amino acid position 96 to be replaced by a serine (S). 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	0.29
BayesDel_addAF	Benign	-0.032	T
BayesDel_noAF	Benign	-0.28
Cadd	Pathogenic	27
Dann	Uncertain	1.0
DEOGEN2	Benign	0.036	T
Eigen	Pathogenic	0.86
Eigen_PC	Pathogenic	0.84
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.044	D
MetaRNN	Uncertain	0.45	T
MetaSVM	Benign	-0.46	T
MutationAssessor	Uncertain	2.1	M
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.23
Sift	Uncertain	0.0050	D
Sift4G	Benign	0.085	T
Polyphen		1.0	D
Vest4		0.49
MutPred		0.54		Gain of relative solvent accessibility (P = 0.0023);
MVP		0.35
MPC		0.57
ClinPred		0.91	D
GERP RS		5.8
Varity_R		0.37

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: chr17-37885837;