1-66972919-G-T

Position:

• chr1-66972919-G-T

Variant summary

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

The NM_001077700.3(MIER1):​c.1029G>T​(p.Glu343Asp) 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 benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MIER1 NM_001077700.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.512

Genes affected

MIER1 (HGNC:29657): (MIER1 transcriptional regulator) This gene encodes a protein that was first identified in Xenopus laevis by its role in a mesoderm induction early response (MIER). The encoded protein functions as a transcriptional regulator. Alternatively spliced transcript variants encode multiple isoforms, some of which lack a C-terminal nuclear localization signal. [provided by RefSeq, May 2013]

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
MIER1	NM_001077700.3	c.1029G>T	p.Glu343Asp	missense_variant	11/14	ENST00000401041.6	NP_001071168.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MIER1	ENST00000401041.6	c.1029G>T	p.Glu343Asp	missense_variant	11/14	2	NM_001077700.3	ENSP00000383820.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 27

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

May 30, 2024

The c.1029G>T (p.E343D) alteration is located in exon 11 (coding exon 11) of the MIER1 gene. This alteration results from a G to T substitution at nucleotide position 1029, causing the glutamic acid (E) at amino acid position 343 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	0.98
BayesDel_addAF	Benign	-0.057	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	.;.;.;.;.;.;.;T
Eigen	Benign	-0.021
Eigen_PC	Benign	-0.059
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.93	D;D;D;D;D;D;D;D
M_CAP	Benign	0.044	D
MetaRNN	Benign	0.34	T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Uncertain	2.2	.;.;.;.;.;.;M;M
PrimateAI	Uncertain	0.72	T
PROVEAN	Uncertain	-2.5	D;D;D;D;D;D;D;D
REVEL	Benign	0.18
Sift	Uncertain	0.012	D;D;D;D;D;D;D;D
Sift4G	Uncertain	0.033	D;D;D;D;D;D;D;D
Vest4		0.58
MVP		0.56
MPC		0.82
ClinPred		0.97	D
GERP RS		0.32
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7
Varity_R		0.44
gMVP		0.39

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.28		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.28		Position offset: -1

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: chr1-67438602;