Variant rs778859599 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The ENST00000262843.11(MID2):c.491G>A(p.Arg164His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000043 in 1,209,093 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 19 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R164G) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.000046 ( 0 hom. 19 hem. )

Consequence

MID2
ENST00000262843.11 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.26

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 -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.320652).

BS2

High Hemizygotes in GnomAdExome4 at 19 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MID2	NM_012216.4 linkuse as main transcript	c.491G>A	p.Arg164His	missense_variant	2/10	ENST00000262843.11	NP_036348.2
MID2	NM_001382751.1 linkuse as main transcript	c.431G>A	p.Arg144His	missense_variant	2/10		NP_001369680.1
MID2	NM_052817.3 linkuse as main transcript	c.491G>A	p.Arg164His	missense_variant	2/10		NP_438112.2
MID2	NM_001382752.1 linkuse as main transcript	c.431G>A	p.Arg144His	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.491G>A	p.Arg164His	missense_variant	2/10	1	NM_012216.4	ENSP00000262843		Q9UJV3-1
MID2	ENST00000443968.2 linkuse as main transcript	c.491G>A	p.Arg164His	missense_variant	2/10	1		ENSP00000413976	P1	Q9UJV3-2
MID2	ENST00000451923.1 linkuse as main transcript	c.431G>A	p.Arg144His	missense_variant	2/2	3		ENSP00000410730

Frequencies

GnomAD3 genomes

AF:

0.0000180

AC:

AN:

111275

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33467

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000377

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000493

AC:

AN:

182515

Hom.:

AF XY:

0.0000596

AC XY:

AN XY:

67079

show subpopulations

Gnomad AFR exome

AF:

0.0000761

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000316

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000246

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000455

AC:

AN:

1097818

Hom.:

Cov.:

AF XY:

0.0000523

AC XY:

AN XY:

363188

show subpopulations

Gnomad4 AFR exome

AF:

0.000152

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000351

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000285

Gnomad4 OTH exome

AF:

0.0000434

GnomAD4 genome

AF:

0.0000180

AC:

AN:

111275

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33467

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000377

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000416

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000346

AC:

ExAC

AF:

0.0000659

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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

Genomic Research Center, Shahid Beheshti University of Medical Sciences

Mar 05, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.38

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.12

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.028

T;T;.

FATHMM_MKL

Uncertain

0.90

LIST_S2

Pathogenic

0.98

D;D;D

M_CAP

Pathogenic

0.70

MetaRNN

Benign

0.32

T;T;T

MetaSVM

Uncertain

0.41

MutationAssessor

Benign

1.9

.;L;L

MutationTaster

Benign

0.99

D;D

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-1.2

N;N;N

REVEL

Uncertain

0.45

Sift

Uncertain

0.0060

D;D;D

Sift4G

Uncertain

0.056

T;D;D

Polyphen

0.99, 0.98

.;D;D

Vest4

0.15, 0.34

MVP

0.83

MPC

1.5

ClinPred

0.22

GERP RS

5.9

Varity_R

0.51

gMVP

0.67

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