dbSNP rs1555905454: MID1:p.Ile12Val (chrX-10567514-T-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_000381.4(MID1):c.34A>G(p.Ile12Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 22)

Consequence

MID1
NM_000381.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.86

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

X-linked Opitz G/BBB syndrome
Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: ClinGen, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics

MID1 links:

ENSG00000291314 (HGNC:):

ENSG00000291314 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MID1	NM_000381.4 link	c.34A>G	p.Ile12Val	missense_variant	Exon 2 of 10	ENST00000317552.9	NP_000372.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
MID1	ENST00000317552.9 link	c.34A>G	p.Ile12Val	missense_variant	Exon 2 of 10	1	NM_000381.4	ENSP00000312678.4
MID1	ENST00000380782.6 link	c.34A>G	p.Ile12Val	missense_variant	Exon 2 of 10	1		ENSP00000370159.1
ENSG00000291314	ENST00000706950.1 link	c.*36A>G		3_prime_UTR_variant	Exon 2 of 2			ENSP00000516670.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 25, 2016

Genetic Services Laboratory, University of Chicago

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.42

BayesDel_addAF

Benign

-0.028

BayesDel_noAF

Benign

-0.28

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.083

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

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.94

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

M_CAP

Uncertain

0.12

MetaRNN

Uncertain

0.49

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

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.33

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

PhyloP100

7.9

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-0.18

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

REVEL

Benign

0.22

Sift

Benign

0.32

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

Sift4G

Benign

0.59

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

Polyphen

0.30

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

Vest4

0.60

MutPred

0.55

Gain of catalytic residue at I12 (P = 0.0511);Gain of catalytic residue at I12 (P = 0.0511);Gain of catalytic residue at I12 (P = 0.0511);Gain of catalytic residue at I12 (P = 0.0511);Gain of catalytic residue at I12 (P = 0.0511);Gain of catalytic residue at I12 (P = 0.0511);Gain of catalytic residue at I12 (P = 0.0511);Gain of catalytic residue at I12 (P = 0.0511);Gain of catalytic residue at I12 (P = 0.0511);Gain of catalytic residue at I12 (P = 0.0511);Gain of catalytic residue at I12 (P = 0.0511);

MVP

0.82

MPC

1.7

ClinPred

0.60

GERP RS

5.6

PromoterAI

0.015

Neutral

(source)

Varity_R

0.26

gMVP

0.73

Mutation Taster

=57/43

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over