X-107905593-G-A

Variant names:

• chrX-107905593-G-A
• rs587777605
• NM_012216.4:c.1040G>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 1P and 4B. PP5 BS2

The NM_012216.4(MID2):​c.1040G>A​(p.Arg347Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000147 in 1,088,323 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 10 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely pathogenic (no stars).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.000015 (0 hom. 10 hem.)
• Consequence: MID2 NM_012216.4 missense
• Clinical Significance: Pathogenic/Likely pathogenic no assertion criteria provided P:2
• Conservation: PhyloP100: 7.68
• Publications: 5 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: Likely_benign. The variant received -3 ACMG points.

• PP5: Variant X-107905593-G-A is Pathogenic according to our data. Variant chrX-107905593-G-A is described in ClinVar as Pathogenic/Likely_pathogenic. ClinVar VariationId is 143857.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High Hemizygotes in GnomAdExome4 at 10 Unknown,XL gene

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MID2	NM_012216.4	MANE Select	c.1040G>A	p.Arg347Gln	missense	Exon 5 of 10	NP_036348.2
	MID2	NM_001382751.1		c.980G>A	p.Arg327Gln	missense	Exon 5 of 10	NP_001369680.1
	MID2	NM_052817.3		c.1040G>A	p.Arg347Gln	missense	Exon 5 of 10	NP_438112.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MID2	ENST00000262843.11	TSL:1 MANE Select	c.1040G>A	p.Arg347Gln	missense	Exon 5 of 10	ENSP00000262843.6
	MID2	ENST00000443968.2	TSL:1	c.1040G>A	p.Arg347Gln	missense	Exon 5 of 10	ENSP00000413976.2
	ENSG00000236064	ENST00000430140.3	TSL:2	n.523-9233C>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD2 exomes AF: 0.0000171 AC: 3 AN: 175099 AF XY: 0.0000332

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000147 AC: 16 AN: 1088323 Hom.: 0 Cov.: 28 AF XY: 0.0000282 AC XY: 10 AN XY: 354551

African (AFR) AF: 0.00 AC: 0 AN: 26059

American (AMR) AF: 0.00 AC: 0 AN: 34058

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19026

East Asian (EAS) AF: 0.00 AC: 0 AN: 29987

South Asian (SAS) AF: 0.000292 AC: 15 AN: 51296

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40347

Middle Eastern (MID) AF: 0.000244 AC: 1 AN: 4100

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 837756

Other (OTH) AF: 0.00 AC: 0 AN: 45694

GnomAD4 genome Cov.: 23

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.0000330 AC: 4

ClinVar

Significance: Pathogenic/Likely pathogenic

Submissions summary: Pathogenic:2

Revision: no assertion criteria provided

Submissions by phenotype

Intellectual disability, X-linked 101 Pathogenic:2

Apr 07, 2025

Medgenome Labs Pvt Ltd

Significance: Likely pathogenic

Review Status: no assertion criteria provided

Collection Method: clinical testing

Jan 01, 2014

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.079	T
BayesDel_noAF	Uncertain	-0.080
CADD	Uncertain	23
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.056	T
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	1.0	D
M_CAP	Pathogenic	0.55	D
MetaRNN	Uncertain	0.43	T
MetaSVM	Benign	-0.53	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		7.7
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.21
Sift	Benign	0.10	T
Sift4G	Benign	0.27	T
Polyphen		1.0	D
Vest4		0.26
MutPred		0.57		Loss of helix (P = 0.0376)
MVP		0.72
MPC		0.97
ClinPred		0.53	D
GERP RS		5.5
Varity_R		0.32
gMVP		0.60
Mutation Taster		=24/76	disease causing (ClinVar)

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: rs587777605; hg19: chrX-107148823;