Variant X-107841155-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_012216.4(MID2):c.490C>T(p.Arg164Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000108 in 1,209,243 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 5 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., 1 hem., cov: 23)

Exomes 𝑓: 0.0000091 ( 0 hom. 4 hem. )

Consequence

MID2
NM_012216.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.753

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 -4 ACMG points.

BS2

High Hemizygotes in GnomAdExome4 at 4 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MID2	NM_012216.4 linkuse as main transcript	c.490C>T	p.Arg164Cys	missense_variant	2/10	ENST00000262843.11	NP_036348.2
MID2	NM_001382751.1 linkuse as main transcript	c.430C>T	p.Arg144Cys	missense_variant	2/10		NP_001369680.1
MID2	NM_052817.3 linkuse as main transcript	c.490C>T	p.Arg164Cys	missense_variant	2/10		NP_438112.2
MID2	NM_001382752.1 linkuse as main transcript	c.430C>T	p.Arg144Cys	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.490C>T	p.Arg164Cys	missense_variant	2/10	1	NM_012216.4	ENSP00000262843		Q9UJV3-1
MID2	ENST00000443968.2 linkuse as main transcript	c.490C>T	p.Arg164Cys	missense_variant	2/10	1		ENSP00000413976	P1	Q9UJV3-2
MID2	ENST00000451923.1 linkuse as main transcript	c.430C>T	p.Arg144Cys	missense_variant	2/2	3		ENSP00000410730

Frequencies

GnomAD3 genomes

AF:

0.0000270

AC:

AN:

111302

Hom.:

Cov.:

AF XY:

0.0000299

AC XY:

AN XY:

33486

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:

0.0000566

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000548

AC:

AN:

182551

Hom.:

AF XY:

0.00

AC XY:

AN XY:

67117

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000911

AC:

AN:

1097941

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

363303

show subpopulations

Gnomad4 AFR exome

AF:

0.0000379

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:

0.0000107

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000270

AC:

AN:

111302

Hom.:

Cov.:

AF XY:

0.0000299

AC XY:

AN XY:

33486

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:

0.0000566

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000189

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

Ambry Genetics

Dec 11, 2023

The c.490C>T (p.R164C) alteration is located in exon 2 (coding exon 2) of the MID2 gene. This alteration results from a C to T substitution at nucleotide position 490, causing the arginine (R) at amino acid position 164 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.72

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

0.12

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.096

T;T;.

FATHMM_MKL

Uncertain

0.89

LIST_S2

Pathogenic

0.99

D;D;D

M_CAP

Pathogenic

0.82

MetaRNN

Uncertain

0.56

D;D;D

MetaSVM

Uncertain

0.58

MutationAssessor

Uncertain

2.4

.;M;M

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.86

PROVEAN

Uncertain

-4.2

D;D;D

REVEL

Uncertain

0.53

Sift

Uncertain

0.0010

D;D;D

Sift4G

Uncertain

0.025

D;D;D

Polyphen

1.0, 1.0

.;D;D

Vest4

0.49, 0.51

MutPred

0.46

.;Loss of catalytic residue at R164 (P = 0.018);Loss of catalytic residue at R164 (P = 0.018);

MVP

0.75

MPC

1.5

ClinPred

0.82

GERP RS

5.9

Varity_R

0.76

gMVP

0.78

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