rs12131222

Variant names:

• chr1-66972852-A-T
• rs12131222
• NM_001077700.3:c.1007-45A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.04
• Publications: 5 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]

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 Gene-Disease associations (from GenCC):

• schneckenbecken dysplasia

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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	c.1007-45A>T		intron_variant	Intron 10 of 13	ENST00000401041.6	NP_001071168.2

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33112 AN: 151874 Hom.: 3958 Cov.: 31

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

GnomAD2 exomes AF: 0.220 AC: 45046 AN: 204366 AF XY: 0.220

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 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.: 11 AF XY: 0.236 AC XY: 102632 AN XY: 435590

African (AFR) AF: 0.171 AC: 3305 AN: 19308

American (AMR) AF: 0.139 AC: 4538 AN: 32628

Ashkenazi Jewish (ASJ) AF: 0.190 AC: 3881 AN: 20374

East Asian (EAS) AF: 0.0924 AC: 3304 AN: 35766

South Asian (SAS) AF: 0.136 AC: 9049 AN: 66566

European-Finnish (FIN) AF: 0.358 AC: 18517 AN: 51764

Middle Eastern (MID) AF: 0.174 AC: 771 AN: 4424

European-Non Finnish (NFE) AF: 0.260 AC: 145697 AN: 560262

Other (OTH) AF: 0.238 AC: 9287 AN: 39052

GnomAD4 genome AF: 0.218 AC: 33116 AN: 151992 Hom.: 3958 Cov.: 31 AF XY: 0.218 AC XY: 16209 AN XY: 74294

African (AFR) AF: 0.164 AC: 6794 AN: 41516

American (AMR) AF: 0.171 AC: 2613 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.177 AC: 615 AN: 3470

East Asian (EAS) AF: 0.123 AC: 636 AN: 5184

South Asian (SAS) AF: 0.126 AC: 608 AN: 4832

European-Finnish (FIN) AF: 0.362 AC: 3824 AN: 10562

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.255 AC: 17322 AN: 67840

Other (OTH) AF: 0.212 AC: 448 AN: 2112

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
PhyloP100		1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12131222; hg19: chr1-67438535; COSMIC: COSV62530780;