dbSNP rs12131222: MIER1:c.1007-45A>T (chr1-66972852-A-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001077700.3(MIER1):c.1007-45A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 982,136 control chromosomes in the GnomAD database, including 29,295 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.22 ( 3958 hom., cov: 31)

Exomes 𝑓: 0.24 ( 25337 hom. )

Consequence

MIER1
NM_001077700.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.04

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.252 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIER1	NM_001077700.3 link	c.1007-45A>T		intron_variant	Intron 10 of 13	ENST00000401041.6	NP_001071168.2	Q8N108-12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MIER1	ENST00000401041.6 link	c.1007-45A>T		intron_variant	Intron 10 of 13	2	NM_001077700.3	ENSP00000383820.1		Q8N108-12

Frequencies

GnomAD3 genomes

AF:

0.218

AC:

33112

AN:

151874

Hom.:

3958

Cov.:

show subpopulations

Gnomad AFR

AF:

0.164

Gnomad AMI

AF:

0.221

Gnomad AMR

AF:

0.171

Gnomad ASJ

AF:

0.177

Gnomad EAS

AF:

0.122

Gnomad SAS

AF:

0.125

Gnomad FIN

AF:

0.362

Gnomad MID

AF:

0.196

Gnomad NFE

AF:

0.255

Gnomad OTH

AF:

0.214

GnomAD3 exomes

AF:

0.220

AC:

45046

AN:

204366

Hom.:

5421

AF XY:

0.220

AC XY:

24650

AN XY:

111794

show subpopulations

Gnomad AFR exome

AF:

0.166

Gnomad AMR exome

AF:

0.132

Gnomad ASJ exome

AF:

0.190

Gnomad EAS exome

AF:

0.125

Gnomad SAS exome

AF:

0.134

Gnomad FIN exome

AF:

0.361

Gnomad NFE exome

AF:

0.256

Gnomad OTH exome

AF:

0.235

GnomAD4 exome

AF:

0.239

AC:

198349

AN:

830144

Hom.:

25337

Cov.:

AF XY:

0.236

AC XY:

102632

AN XY:

435590

show subpopulations

Gnomad4 AFR exome

AF:

0.171

Gnomad4 AMR exome

AF:

0.139

Gnomad4 ASJ exome

AF:

0.190

Gnomad4 EAS exome

AF:

0.0924

Gnomad4 SAS exome

AF:

0.136

Gnomad4 FIN exome

AF:

0.358

Gnomad4 NFE exome

AF:

0.260

Gnomad4 OTH exome

AF:

0.238

GnomAD4 genome

AF:

0.218

AC:

33116

AN:

151992

Hom.:

3958

Cov.:

AF XY:

0.218

AC XY:

16209

AN XY:

74294

show subpopulations

Gnomad4 AFR

AF:

0.164

Gnomad4 AMR

AF:

0.171

Gnomad4 ASJ

AF:

0.177

Gnomad4 EAS

AF:

0.123

Gnomad4 SAS

AF:

0.126

Gnomad4 FIN

AF:

0.362

Gnomad4 NFE

AF:

0.255

Gnomad4 OTH

AF:

0.212

Alfa

AF:

0.218

Hom.:

718

Bravo

AF:

0.204

Asia WGS

AF:

0.130

AC:

452

AN:

3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

7.6

DANN

Benign

0.75

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over