X-107841067-C-G

Position:

chrX-107841067-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_012216.4(MID2):c.402C>G(p.Ser134Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,209,458 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. 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: 𝑓 0.0000090 ( 0 hom., 1 hem., cov: 23)

Exomes 𝑓: 0.0000018 ( 0 hom. 0 hem. )

Consequence

MID2
NM_012216.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.27

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16269973).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MID2	NM_012216.4 linkuse as main transcript	c.402C>G	p.Ser134Arg	missense_variant	2/10	ENST00000262843.11	NP_036348.2
MID2	NM_001382751.1 linkuse as main transcript	c.342C>G	p.Ser114Arg	missense_variant	2/10		NP_001369680.1
MID2	NM_052817.3 linkuse as main transcript	c.402C>G	p.Ser134Arg	missense_variant	2/10		NP_438112.2
MID2	NM_001382752.1 linkuse as main transcript	c.342C>G	p.Ser114Arg	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.402C>G	p.Ser134Arg	missense_variant	2/10	1	NM_012216.4	ENSP00000262843		Q9UJV3-1
MID2	ENST00000443968.2 linkuse as main transcript	c.402C>G	p.Ser134Arg	missense_variant	2/10	1		ENSP00000413976	P1	Q9UJV3-2
MID2	ENST00000451923.1 linkuse as main transcript	c.342C>G	p.Ser114Arg	missense_variant	2/2	3		ENSP00000410730

Frequencies

GnomAD3 genomes

AF:

0.00000898

AC:

AN:

111317

Hom.:

Cov.:

AF XY:

0.0000298

AC XY:

AN XY:

33531

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:

0.00000182

AC:

AN:

1098141

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

363499

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000237

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000898

AC:

AN:

111317

Hom.:

Cov.:

AF XY:

0.0000298

AC XY:

AN XY:

33531

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:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Apr 18, 2022

Variant summary: MID2 c.402C>G (p.Ser134Arg) results in a non-conservative amino acid change located in the B-box-type zinc finger domain (IPR000315) of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant was absent in 183020 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.402C>G in individuals affected with Intellectual Disability, X-Linked 101 and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.40

BayesDel_addAF

Benign

-0.040

BayesDel_noAF

Benign

-0.30

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.021

T;T;.

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.87

D;D;D

M_CAP

Benign

0.071

MetaRNN

Benign

0.16

T;T;T

MetaSVM

Benign

-0.47

MutationAssessor

Benign

1.6

.;L;L

MutationTaster

Benign

0.97

D;D

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-1.2

N;N;N

REVEL

Benign

0.28

Sift

Benign

0.35

T;T;T

Sift4G

Benign

0.46

T;T;T

Polyphen

0.39, 0.78

.;B;P

Vest4

0.14, 0.19

MutPred

0.26

.;Gain of MoRF binding (P = 0.0305);Gain of MoRF binding (P = 0.0305);

MVP

0.58

MPC

0.58

ClinPred

0.42

GERP RS

3.6

Varity_R

0.24

gMVP

0.34

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