NM_012216.4:c.816+4364A>G

Variant names:

• chrX-107859068-A-G
• rs5962901
• NM_012216.4:c.816+4364A>G

Variant summary

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

The NM_012216.4(MID2):​c.816+4364A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.071 in 111,748 control chromosomes in the GnomAD database, including 717 homozygotes. There are 2,122 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 0.071 (717 hom., 2122 hem., cov: 22)
• Consequence: MID2 NM_012216.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.15
• Publications: 1 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.24 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012216.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MID2	NM_012216.4	MANE Select	c.816+4364A>G		intron	N/A	NP_036348.2	Q9UJV3-1
	MID2	NM_001382751.1		c.756+4364A>G		intron	N/A	NP_001369680.1
	MID2	NM_052817.3		c.816+4364A>G		intron	N/A	NP_438112.2	Q9UJV3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MID2	ENST00000262843.11	TSL:1 MANE Select	c.816+4364A>G		intron	N/A	ENSP00000262843.6	Q9UJV3-1
	MID2	ENST00000443968.2	TSL:1	c.816+4364A>G		intron	N/A	ENSP00000413976.2	Q9UJV3-2
	MID2	ENST00000921443.1		c.720+17683A>G		intron	N/A	ENSP00000591502.1

Frequencies

GnomAD3 genomes AF: 0.0710 AC: 7927 AN: 111698 Hom.: 718 Cov.: 22

Gnomad AFR AF: 0.245

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0306

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00113

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00418

Gnomad NFE AF: 0.000902

Gnomad OTH AF: 0.0614

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

GnomAD4 genome AF: 0.0710 AC: 7933 AN: 111748 Hom.: 717 Cov.: 22 AF XY: 0.0625 AC XY: 2122 AN XY: 33940

African (AFR) AF: 0.244 AC: 7466 AN: 30568

American (AMR) AF: 0.0306 AC: 323 AN: 10553

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2655

East Asian (EAS) AF: 0.00 AC: 0 AN: 3591

South Asian (SAS) AF: 0.00113 AC: 3 AN: 2655

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6088

Middle Eastern (MID) AF: 0.00461 AC: 1 AN: 217

European-Non Finnish (NFE) AF: 0.000902 AC: 48 AN: 53216

Other (OTH) AF: 0.0606 AC: 92 AN: 1518

Alfa AF: 0.0285 Hom.: 353

Bravo AF: 0.0811

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.1
DANN	Benign	0.82
PhyloP100		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs5962901; hg19: chrX-107102298;