X-10567514-T-C

Position:

• chrX-10567514-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.86

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]

(HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MID1	NM_000381.4	c.34A>G	p.Ile12Val	missense_variant	2/10	ENST00000317552.9	NP_000372.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MID1	ENST00000317552.9	c.34A>G	p.Ile12Val	missense_variant	2/10	1	NM_000381.4	ENSP00000312678	P1
	ENST00000706950.1	c.*36A>G		3_prime_UTR_variant	2/2			ENSP00000516670	P1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 22

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Apr 25, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Benign	-0.028	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.083	T;T;T;T;T;T;.;.;T;T;T
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.94	D;.;.;.;.;.;D;D;D;D;D
M_CAP	Uncertain	0.12	D
MetaRNN	Uncertain	0.49	T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.33	N;N;N;N;N;N;N;.;.;.;.
MutationTaster	Benign	1.0	D;D;D;D;D;D;D
PrimateAI	Pathogenic	0.84	D
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	D
GERP RS		5.6
Varity_R		0.26
gMVP		0.73

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

Other links and lift over

dbSNP: rs1555905454; hg19: chrX-10535554;