1-66984641-A-G

Position:

• chr1-66984641-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001077700.3(MIER1):​c.1439A>G​(p.Asn480Ser) variant causes a missense change. 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: 6.79

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]

SLC35D1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35016268).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MIER1	NM_001077700.3	c.1439A>G	p.Asn480Ser	missense_variant	14/14	ENST00000401041.6	NP_001071168.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MIER1	ENST00000401041.6	c.1439A>G	p.Asn480Ser	missense_variant	14/14	2	NM_001077700.3	ENSP00000383820

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 10, 2024

The c.1439A>G (p.N480S) alteration is located in exon 14 (coding exon 14) of the MIER1 gene. This alteration results from a A to G substitution at nucleotide position 1439, causing the asparagine (N) at amino acid position 480 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	0.096
BayesDel_addAF	Benign	-0.018	T
BayesDel_noAF	Benign	-0.26
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.086	.;.;.;T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.97	D;D;D;D
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.35	T;T;T;T
MetaSVM	Benign	-0.80	T
MutationAssessor	Uncertain	2.6	.;.;.;M
MutationTaster	Benign	1.0	D;D;D;D;D;D;D;D
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-2.1	N;N;N;N
REVEL	Benign	0.21
Sift	Pathogenic	0.0	D;T;T;T
Sift4G	Uncertain	0.025	D;T;T;T
Vest4		0.68
MVP		0.81
MPC		0.76
ClinPred		0.97	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.36
gMVP		0.27

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-67450324;