rs742584

Variant names:

• chrX-107930939-T-A
• rs742584
• NM_012216.4:c.*3866T>A

Variant summary

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

The NM_012216.4(MID2):​c.*3866T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 111,717 control chromosomes in the GnomAD database, including 945 homozygotes. There are 4,541 hemizygotes in GnomAD. 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 0.14 (945 hom., 4541 hem., cov: 23)
• Consequence: MID2 NM_012216.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.92
• Publications: 4 publications found

Genes affected

MID2 (HGNC:7096): (midline 2) The protein encoded by this gene is a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. The protein localizes to microtubular structures in the cytoplasm. Alternate splicing of this gene results in two transcript variants encoding different isoforms. [provided by RefSeq, Feb 2009]

MID2 Gene-Disease associations (from GenCC):

• non-syndromic X-linked intellectual disability

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet
• intellectual disability, X-linked 101

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ENSG00000236064 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.193 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MID2	NM_012216.4	c.*3866T>A		3_prime_UTR_variant	Exon 10 of 10	ENST00000262843.11	NP_036348.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MID2	ENST00000262843.11	c.*3866T>A		3_prime_UTR_variant	Exon 10 of 10	1	NM_012216.4	ENSP00000262843.6

Frequencies

GnomAD3 genomes AF: 0.140 AC: 15639 AN: 111661 Hom.: 944 Cov.: 23

Gnomad AFR AF: 0.197

Gnomad AMI AF: 0.239

Gnomad AMR AF: 0.110

Gnomad ASJ AF: 0.216

Gnomad EAS AF: 0.166

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.300

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.144

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.140 AC: 15648 AN: 111717 Hom.: 945 Cov.: 23 AF XY: 0.134 AC XY: 4541 AN XY: 33939

African (AFR) AF: 0.197 AC: 6060 AN: 30779

American (AMR) AF: 0.111 AC: 1168 AN: 10553

Ashkenazi Jewish (ASJ) AF: 0.216 AC: 568 AN: 2632

East Asian (EAS) AF: 0.166 AC: 588 AN: 3539

South Asian (SAS) AF: 0.136 AC: 365 AN: 2684

European-Finnish (FIN) AF: 0.107 AC: 645 AN: 6055

Middle Eastern (MID) AF: 0.297 AC: 63 AN: 212

European-Non Finnish (NFE) AF: 0.110 AC: 5812 AN: 53065

Other (OTH) AF: 0.143 AC: 217 AN: 1520

Alfa AF: 0.129 Hom.: 715

Bravo AF: 0.147

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	5.4
DANN	Benign	0.52
PhyloP100		1.9

Splicing

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

Other links and lift over

dbSNP: rs742584; hg19: chrX-107174169;