Variant X-107840845-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_012216.4(MID2):c.180A>C(p.Ser60=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0698 in 1,209,290 control chromosomes in the GnomAD database, including 2,463 homozygotes. There are 27,770 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 585 hom., 3141 hem., cov: 22)

Exomes 𝑓: 0.067 ( 1878 hom. 24629 hem. )

Consequence

MID2
NM_012216.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.279

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP6

Variant X-107840845-A-C is Benign according to our data. Variant chrX-107840845-A-C is described in ClinVar as [Benign]. Clinvar id is 1321169.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.279 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MID2	NM_012216.4 linkuse as main transcript	c.180A>C	p.Ser60=	synonymous_variant	2/10	ENST00000262843.11	NP_036348.2
MID2	NM_001382751.1 linkuse as main transcript	c.120A>C	p.Ser40=	synonymous_variant	2/10		NP_001369680.1
MID2	NM_052817.3 linkuse as main transcript	c.180A>C	p.Ser60=	synonymous_variant	2/10		NP_438112.2
MID2	NM_001382752.1 linkuse as main transcript	c.120A>C	p.Ser40=	synonymous_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.180A>C	p.Ser60=	synonymous_variant	2/10	1	NM_012216.4	ENSP00000262843		Q9UJV3-1
MID2	ENST00000443968.2 linkuse as main transcript	c.180A>C	p.Ser60=	synonymous_variant	2/10	1		ENSP00000413976	P1	Q9UJV3-2
MID2	ENST00000451923.1 linkuse as main transcript	c.120A>C	p.Ser40=	synonymous_variant	2/2	3		ENSP00000410730

Frequencies

GnomAD3 genomes

AF:

0.100

AC:

11131

AN:

111023

Hom.:

584

Cov.:

AF XY:

0.0940

AC XY:

3126

AN XY:

33253

show subpopulations

Gnomad AFR

AF:

0.192

Gnomad AMI

AF:

0.228

Gnomad AMR

AF:

0.0624

Gnomad ASJ

AF:

0.0436

Gnomad EAS

AF:

0.107

Gnomad SAS

AF:

0.0949

Gnomad FIN

AF:

0.0651

Gnomad MID

AF:

0.0917

Gnomad NFE

AF:

0.0611

Gnomad OTH

AF:

0.0694

GnomAD3 exomes

AF:

0.0775

AC:

14208

AN:

183300

Hom.:

448

AF XY:

0.0761

AC XY:

5163

AN XY:

67804

show subpopulations

Gnomad AFR exome

AF:

0.196

Gnomad AMR exome

AF:

0.0556

Gnomad ASJ exome

AF:

0.0476

Gnomad EAS exome

AF:

0.106

Gnomad SAS exome

AF:

0.0894

Gnomad FIN exome

AF:

0.0698

Gnomad NFE exome

AF:

0.0628

Gnomad OTH exome

AF:

0.0704

GnomAD4 exome

AF:

0.0668

AC:

73308

AN:

1098216

Hom.:

1878

Cov.:

AF XY:

0.0677

AC XY:

24629

AN XY:

363574

show subpopulations

Gnomad4 AFR exome

AF:

0.200

Gnomad4 AMR exome

AF:

0.0548

Gnomad4 ASJ exome

AF:

0.0500

Gnomad4 EAS exome

AF:

0.108

Gnomad4 SAS exome

AF:

0.0891

Gnomad4 FIN exome

AF:

0.0696

Gnomad4 NFE exome

AF:

0.0595

Gnomad4 OTH exome

AF:

0.0793

GnomAD4 genome

AF:

0.100

AC:

11149

AN:

111074

Hom.:

585

Cov.:

AF XY:

0.0943

AC XY:

3141

AN XY:

33314

show subpopulations

Gnomad4 AFR

AF:

0.192

Gnomad4 AMR

AF:

0.0628

Gnomad4 ASJ

AF:

0.0436

Gnomad4 EAS

AF:

0.107

Gnomad4 SAS

AF:

0.0968

Gnomad4 FIN

AF:

0.0651

Gnomad4 NFE

AF:

0.0612

Gnomad4 OTH

AF:

0.0685

Alfa

AF:

0.0717

Hom.:

2441

Bravo

AF:

0.106

EpiCase

AF:

0.0635

EpiControl

AF:

0.0675

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Intellectual disability, X-linked 101

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

0.55

DANN

Benign

0.64

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