Variant chrX-10567205-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_000381.4(MID1):c.343G>A(p.Glu115Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000992 in 1,209,486 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., 1 hem., cov: 22)

Exomes 𝑓: 0.0000082 ( 0 hom. 3 hem. )

Consequence

MID1
NM_000381.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.02

Variant links:

Genes affected

MID1 (HGNC:7095): (midline 1) The protein encoded by this gene is a member of the tripartite motif (TRIM) family, also known as the 'RING-B box-coiled coil' (RBCC) subgroup of RING finger proteins. 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. This protein forms homodimers which associate with microtubules in the cytoplasm. The protein is likely involved in the formation of multiprotein structures acting as anchor points to microtubules. Mutations in this gene have been associated with the X-linked form of Opitz syndrome, which is characterized by midline abnormalities such as cleft lip, laryngeal cleft, heart defects, hypospadias, and agenesis of the corpus callosum. This gene was also the first example of a gene subject to X inactivation in human while escaping it in mouse. Alternative promoter use, alternative splicing and alternative polyadenylation result in multiple transcript variants that have different tissue specificities. [provided by RefSeq, Dec 2016]

MID1 links:

ENSG00000291314 (HGNC:):

ENSG00000291314 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High Hemizygotes in GnomAdExome4 at 3 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MID1	NM_000381.4 linkuse as main transcript	c.343G>A	p.Glu115Lys	missense_variant	2/10	ENST00000317552.9	NP_000372.1	O15344-1A0A024RBV4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MID1	ENST00000317552.9 linkuse as main transcript	c.343G>A	p.Glu115Lys	missense_variant	2/10	1	NM_000381.4	ENSP00000312678.4	O15344-1
MID1	ENST00000380782.6 linkuse as main transcript	c.343G>A	p.Glu115Lys	missense_variant	2/10	1		ENSP00000370159.1	O15344-2
ENSG00000291314	ENST00000706950.1 linkuse as main transcript	c.*345G>A		3_prime_UTR_variant	2/2			ENSP00000516670.1	A0A9L9PXS7

Frequencies

GnomAD3 genomes

AF:

0.0000269

AC:

AN:

111370

Hom.:

Cov.:

AF XY:

0.0000298

AC XY:

AN XY:

33554

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:

0.00000545

AC:

AN:

183349

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

67803

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.0000122

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000820

AC:

AN:

1098116

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

363472

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:

0.0000107

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000269

AC:

AN:

111370

Hom.:

Cov.:

AF XY:

0.0000298

AC XY:

AN XY:

33554

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

Alfa

AF:

0.000138

Hom.:

Bravo

AF:

0.0000227

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Uncertain

0.10

BayesDel_noAF

Benign

-0.090

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.23

T;T;T;T;T;T;.;.;T;T;T

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.93

D;.;.;.;.;.;D;D;D;D;D

M_CAP

Pathogenic

0.89

MetaRNN

Uncertain

0.46

T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Uncertain

0.057

MutationAssessor

Benign

1.6

L;L;L;L;L;L;L;.;.;.;.

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-0.93

N;N;N;N;N;N;N;N;.;.;N

REVEL

Uncertain

0.46

Sift

Benign

0.14

T;T;T;T;T;T;T;T;.;.;T

Sift4G

Uncertain

0.018

D;D;D;D;D;D;D;.;D;T;.

Polyphen

0.28

B;B;B;B;B;B;P;B;.;.;B

Vest4

0.25

MutPred

0.35

Gain of ubiquitination at E115 (P = 0.0117);Gain of ubiquitination at E115 (P = 0.0117);Gain of ubiquitination at E115 (P = 0.0117);Gain of ubiquitination at E115 (P = 0.0117);Gain of ubiquitination at E115 (P = 0.0117);Gain of ubiquitination at E115 (P = 0.0117);Gain of ubiquitination at E115 (P = 0.0117);Gain of ubiquitination at E115 (P = 0.0117);Gain of ubiquitination at E115 (P = 0.0117);Gain of ubiquitination at E115 (P = 0.0117);Gain of ubiquitination at E115 (P = 0.0117);

MVP

0.81

MPC

1.0

ClinPred

0.45

GERP RS

5.6

Varity_R

0.59

gMVP

0.83

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over