X-107841038-A-G

Position:

• chrX-107841038-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_012216.4(MID2):​c.373A>G​(p.Thr125Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: MID2 NM_012216.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.06

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.052385747).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MID2	NM_012216.4	c.373A>G	p.Thr125Ala	missense_variant	2/10	ENST00000262843.11	NP_036348.2
MID2	NM_001382751.1	c.313A>G	p.Thr105Ala	missense_variant	2/10		NP_001369680.1
MID2	NM_052817.3	c.373A>G	p.Thr125Ala	missense_variant	2/10		NP_438112.2
MID2	NM_001382752.1	c.313A>G	p.Thr105Ala	missense_variant	2/10		NP_001369681.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MID2	ENST00000262843.11	c.373A>G	p.Thr125Ala	missense_variant	2/10	1	NM_012216.4	ENSP00000262843
MID2	ENST00000443968.2	c.373A>G	p.Thr125Ala	missense_variant	2/10	1		ENSP00000413976	P1
MID2	ENST00000451923.1	c.313A>G	p.Thr105Ala	missense_variant	2/2	3		ENSP00000410730

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 23

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Intellectual disability, X-linked 101 Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital

May 31, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	18
DANN	Benign	0.30
DEOGEN2	Benign	0.0021	T;T;.
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.64	T;T;T
M_CAP	Uncertain	0.096	D
MetaRNN	Benign	0.052	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-2.1	.;N;N
MutationTaster	Benign	0.87	N;N
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	0.45	N;N;N
REVEL	Benign	0.11
Sift	Benign	1.0	T;T;T
Sift4G	Benign	0.90	T;T;T
Polyphen		0.0060, 0.0	.;B;B
Vest4		0.050, 0.057
MutPred		0.14		.;Loss of phosphorylation at T125 (P = 0.0022);Loss of phosphorylation at T125 (P = 0.0022);
MVP		0.59
MPC		0.46
ClinPred		0.63	D
GERP RS		5.9
Varity_R		0.12
gMVP		0.26

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

Publications

LitVar

Other links and lift over

dbSNP: rs1931331739; hg19: chrX-107084268;