1-66958953-C-G

Variant names:

• chr1-66958953-C-G
• rs368057027
• NM_001077700.3:c.604C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001077700.3(MIER1):​c.604C>G​(p.Arg202Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,552 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R202H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: MIER1 NM_001077700.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.04
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001077700.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIER1	NM_001077700.3	MANE Select	c.604C>G	p.Arg202Gly	missense	Exon 6 of 14	NP_001071168.2	Q8N108-12
	MIER1	NM_001350530.2		c.715C>G	p.Arg239Gly	missense	Exon 8 of 16	NP_001337459.1
	MIER1	NM_001146110.2		c.496C>G	p.Arg166Gly	missense	Exon 7 of 15	NP_001139582.1	Q8N108-13

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIER1	ENST00000401041.6	TSL:2 MANE Select	c.604C>G	p.Arg202Gly	missense	Exon 6 of 14	ENSP00000383820.1	Q8N108-12
	MIER1	ENST00000357692.6	TSL:1	c.496C>G	p.Arg166Gly	missense	Exon 7 of 15	ENSP00000350321.2	Q8N108-13
	MIER1	ENST00000355356.3	TSL:1	c.445C>G	p.Arg149Gly	missense	Exon 5 of 13	ENSP00000347514.3	Q8N108-11

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460552 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 726708

African (AFR) AF: 0.00 AC: 0 AN: 33442

American (AMR) AF: 0.00 AC: 0 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26102

East Asian (EAS) AF: 0.00 AC: 0 AN: 39630

South Asian (SAS) AF: 0.00 AC: 0 AN: 86170

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53382

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111046

Other (OTH) AF: 0.00 AC: 0 AN: 60312

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.076	T
Eigen	Uncertain	0.66
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.026	D
MetaRNN	Uncertain	0.58	D
MetaSVM	Benign	-0.87	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		6.0
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.15
Sift	Benign	0.15	T
Sift4G	Benign	0.11	T
Vest4		0.66
MVP		0.46
MPC		0.86
ClinPred		0.86	D
GERP RS		5.6
Varity_R		0.31
gMVP		0.28
Mutation Taster		=18/82	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs368057027; hg19: chr1-67424636;