rs387906719

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5

The NM_000381.4(MID1):​c.712G>T​(p.Glu238Ter) variant causes a stop gained change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 21)

Consequence

MID1
NM_000381.4 stop_gained

Scores

3
1
1

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 7.15
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]

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ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 11 ACMG points.

PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant X-10523136-C-A is Pathogenic according to our data. Variant chrX-10523136-C-A is described in ClinVar as [Pathogenic]. Clinvar id is 29975.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-10523136-C-A is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MID1NM_000381.4 linkuse as main transcriptc.712G>T p.Glu238Ter stop_gained 3/10 ENST00000317552.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MID1ENST00000317552.9 linkuse as main transcriptc.712G>T p.Glu238Ter stop_gained 3/101 NM_000381.4 P1O15344-1

Frequencies

GnomAD3 genomes
Cov.:
21
GnomAD4 exome
Cov.:
29
GnomAD4 genome
Cov.:
21

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

X-linked Opitz G/BBB syndrome Pathogenic:1
Pathogenic, no assertion criteria providedliterature onlyOMIMMay 01, 2011- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.74
D
BayesDel_noAF
Pathogenic
0.65
CADD
Pathogenic
37
DANN
Uncertain
1.0
FATHMM_MKL
Pathogenic
0.98
D
MutationTaster
Benign
1.0
A;A;A;A;A;A;A
Vest4
0.91
GERP RS
5.0

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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.

Other links and lift over

dbSNP: rs387906719; hg19: chrX-10491176; API