X-107841113-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_012216.4(MID2):c.448G>T(p.Ala150Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 9.96

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MID2	NM_012216.4	c.448G>T	p.Ala150Ser	missense_variant	2/10	ENST00000262843.11
MID2	NM_001382751.1	c.388G>T	p.Ala130Ser	missense_variant	2/10
MID2	NM_052817.3	c.448G>T	p.Ala150Ser	missense_variant	2/10
MID2	NM_001382752.1	c.388G>T	p.Ala130Ser	missense_variant	2/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MID2	ENST00000262843.11	c.448G>T	p.Ala150Ser	missense_variant	2/10	1	NM_012216.4
MID2	ENST00000443968.2	c.448G>T	p.Ala150Ser	missense_variant	2/10	1		P1
MID2	ENST00000451923.1	c.388G>T	p.Ala130Ser	missense_variant	2/2	3

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 23

Bravo AF: 0.00000756

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000149 AC: 1

ExAC AF: 0.00000824 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center

Mar 20, 2024

PM2 -

Intellectual disability, X-linked 101 Uncertain:1

Uncertain significance, criteria provided, single submitter

research

HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology

Dec 09, 2014

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.69
BayesDel_addAF	Pathogenic	0.34	D
BayesDel_noAF	Pathogenic	0.25
Cadd	Uncertain	25
Dann	Uncertain	1.0
DEOGEN2	Benign	0.050	T;T;.
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.89	D;D;D
M_CAP	Pathogenic	0.88	D
MetaRNN	Uncertain	0.74	D;D;D
MetaSVM	Uncertain	0.71	D
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.78	T
PROVEAN	Uncertain	-2.5	D;N;N
REVEL	Pathogenic	0.65
Sift	Benign	0.27	T;T;T
Sift4G	Benign	0.068	T;D;D
Polyphen		1.0, 1.0	.;D;D
Vest4		0.71, 0.81
MVP		0.95
MPC		1.3
ClinPred		0.89	D
GERP RS		5.9
Varity_R		0.53
gMVP		0.81

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: rs375785745; hg19: chrX-107084343;