Variant chrX-107840973-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP3_ModerateBS2

The NM_012216.4(MID2):c.308T>G(p.Ile103Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,209,712 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000090 ( 0 hom., 1 hem., cov: 22)

Exomes 𝑓: 0.0000046 ( 0 hom. 2 hem. )

Consequence

MID2
NM_012216.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.02

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.877

BS2

High Hemizygotes in GnomAdExome4 at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MID2	NM_012216.4 linkuse as main transcript	c.308T>G	p.Ile103Ser	missense_variant	2/10	ENST00000262843.11	NP_036348.2
MID2	NM_001382751.1 linkuse as main transcript	c.248T>G	p.Ile83Ser	missense_variant	2/10		NP_001369680.1
MID2	NM_052817.3 linkuse as main transcript	c.308T>G	p.Ile103Ser	missense_variant	2/10		NP_438112.2
MID2	NM_001382752.1 linkuse as main transcript	c.248T>G	p.Ile83Ser	missense_variant	2/10		NP_001369681.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MID2	ENST00000262843.11 linkuse as main transcript	c.308T>G	p.Ile103Ser	missense_variant	2/10	1	NM_012216.4	ENSP00000262843		Q9UJV3-1
MID2	ENST00000443968.2 linkuse as main transcript	c.308T>G	p.Ile103Ser	missense_variant	2/10	1		ENSP00000413976	P1	Q9UJV3-2
MID2	ENST00000451923.1 linkuse as main transcript	c.248T>G	p.Ile83Ser	missense_variant	2/2	3		ENSP00000410730

Frequencies

GnomAD3 genomes

AF:

0.00000897

AC:

AN:

111505

Hom.:

Cov.:

AF XY:

0.0000297

AC XY:

AN XY:

33663

show subpopulations

Gnomad AFR

AF:

0.0000327

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000455

AC:

AN:

1098207

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

363561

show subpopulations

Gnomad4 AFR exome

AF:

0.000114

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000185

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000217

GnomAD4 genome

AF:

0.00000897

AC:

AN:

111505

Hom.:

Cov.:

AF XY:

0.0000297

AC XY:

AN XY:

33663

show subpopulations

Gnomad4 AFR

AF:

0.0000327

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Intellectual disability, X-linked 101

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Baylor Genetics

Dec 23, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

1.0

BayesDel_addAF

Pathogenic

0.31

BayesDel_noAF

Pathogenic

0.21

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.12

T;T;.

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Pathogenic

1.0

D;D;D

M_CAP

Pathogenic

0.68

MetaRNN

Pathogenic

0.88

D;D;D

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.6

.;M;M

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.89

PROVEAN

Pathogenic

-5.4

D;D;D

REVEL

Pathogenic

0.67

Sift

Pathogenic

0.0

D;D;D

Sift4G

Uncertain

0.0030

D;D;D

Polyphen

1.0

.;D;D

Vest4

0.94, 0.89

MutPred

0.62

.;Gain of disorder (P = 0.0056);Gain of disorder (P = 0.0056);

MVP

0.92

MPC

1.6

ClinPred

1.0

GERP RS

5.9

Varity_R

0.91

gMVP

0.90

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over