Variant chr1-66984580-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001077700.3(MIER1):c.1378T>C(p.Ser460Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00277 in 1,588,110 control chromosomes in the GnomAD database, including 7 homozygotes. 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.0017 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0029 ( 7 hom. )

Consequence

MIER1
NM_001077700.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.16

Variant links:

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]

MIER1 links:

SLC35D1 (HGNC:20800): (solute carrier family 35 member D1) Glycosylation of cellular glycoconjugates occurs in the endoplasmic reticulum (ER) and Golgi compartment, and requires transport of nucleotide sugars from the cytosol into the lumen of the ER and Golgi by specific transporters. The protein encoded by this gene resides in the ER, and transports both UDP-glucuronic acid (UDP-GlcA) and UDP-N-acetylgalactosamine (UDP-GalNAc) from the cytoplasm to the ER lumen. It may participate in glucuronidation and/or chondroitin sulfate biosynthesis. Mutations in this gene are associated with Schneckenbecken dysplasia.[provided by RefSeq, Sep 2009]

SLC35D1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010276109).

BP6

Variant 1-66984580-T-C is Benign according to our data. Variant chr1-66984580-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3024943.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 7 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MIER1	NM_001077700.3 linkuse as main transcript	c.1378T>C	p.Ser460Pro	missense_variant	14/14	ENST00000401041.6	NP_001071168.2	Q8N108-12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MIER1	ENST00000401041.6 linkuse as main transcript	c.1378T>C	p.Ser460Pro	missense_variant	14/14	2	NM_001077700.3	ENSP00000383820.1		Q8N108-12

Frequencies

GnomAD3 genomes

AF:

0.00168

AC:

256

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000555

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00319

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.00191

AC:

434

AN:

226910

Hom.:

AF XY:

0.00201

AC XY:

247

AN XY:

123156

show subpopulations

Gnomad AFR exome

AF:

0.000398

Gnomad AMR exome

AF:

0.000420

Gnomad ASJ exome

AF:

0.00237

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000289

Gnomad NFE exome

AF:

0.00357

Gnomad OTH exome

AF:

0.00168

GnomAD4 exome

AF:

0.00289

AC:

4144

AN:

1435776

Hom.:

Cov.:

AF XY:

0.00280

AC XY:

1999

AN XY:

713298

show subpopulations

Gnomad4 AFR exome

AF:

0.000251

Gnomad4 AMR exome

AF:

0.000366

Gnomad4 ASJ exome

AF:

0.00291

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000360

Gnomad4 NFE exome

AF:

0.00356

Gnomad4 OTH exome

AF:

0.00174

GnomAD4 genome

AF:

0.00168

AC:

256

AN:

152334

Hom.:

Cov.:

AF XY:

0.00125

AC XY:

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.000553

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.00319

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.00321

Hom.:

Bravo

AF:

0.00181

TwinsUK

AF:

0.00458

AC:

ALSPAC

AF:

0.00337

AC:

ESP6500AA

AF:

0.000276

AC:

ESP6500EA

AF:

0.00233

AC:

ExAC

AF:

0.00181

AC:

219

EpiCase

AF:

0.00280

EpiControl

AF:

0.00321

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2024

MIER1: BP4, BS1 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.22

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.035

.;.;.;.;.;.;.;T

Eigen

Benign

-0.097

Eigen_PC

Benign

-0.027

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.96

D;D;D;D;D;D;D;D

M_CAP

Benign

0.034

MetaRNN

Benign

0.010

T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.2

.;.;.;.;.;.;L;L

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-1.7

N;N;N;N;N;N;N;N

REVEL

Benign

0.26

Sift

Uncertain

0.010

D;D;T;D;D;D;D;T

Sift4G

Benign

0.11

T;T;T;T;T;T;T;T

Vest4

0.33

MVP

0.73

MPC

0.45

ClinPred

0.032

GERP RS

4.5

Varity_R

0.33

gMVP

0.31

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over