Variant X-10567205-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_000381.4(MID1):c.343G>C(p.Glu115Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 22)

Exomes 𝑓: 9.1e-7 ( 0 hom. 1 hem. )

Failed GnomAD Quality Control

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:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.40498257).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MID1	NM_000381.4 linkuse as main transcript	c.343G>C	p.Glu115Gln	missense_variant	2/10	ENST00000317552.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MID1	ENST00000317552.9 linkuse as main transcript	c.343G>C	p.Glu115Gln	missense_variant	2/10	1	NM_000381.4	P1	O15344-1
	ENST00000706950.1 linkuse as main transcript	c.*345G>C		3_prime_UTR_variant	2/2			P1

Frequencies

GnomAD3 genomes

Cov.:

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:

0.0000365

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

Data not reliable, filtered out with message: AS_VQSR

AF:

9.11e-7

AC:

AN:

1098116

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

363472

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000284

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Uncertain

0.023

BayesDel_noAF

Benign

-0.20

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.22

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

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.86

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

M_CAP

Pathogenic

0.83

MetaRNN

Benign

0.40

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

MetaSVM

Uncertain

0.26

MutationAssessor

Benign

1.8

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

MutationTaster

Benign

1.0

D;D;D;D;D;D;D

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-0.63

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

REVEL

Uncertain

0.44

Sift

Benign

0.18

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

Sift4G

Benign

0.070

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

Polyphen

0.38

B;B;B;B;B;B;B;B;.;.;B

Vest4

0.27

MutPred

0.22

Gain of methylation at K116 (P = 0.0765);Gain of methylation at K116 (P = 0.0765);Gain of methylation at K116 (P = 0.0765);Gain of methylation at K116 (P = 0.0765);Gain of methylation at K116 (P = 0.0765);Gain of methylation at K116 (P = 0.0765);Gain of methylation at K116 (P = 0.0765);Gain of methylation at K116 (P = 0.0765);Gain of methylation at K116 (P = 0.0765);Gain of methylation at K116 (P = 0.0765);Gain of methylation at K116 (P = 0.0765);

MVP

0.85

MPC

1.1

ClinPred

0.34

GERP RS

5.6

Varity_R

0.35

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over