X-10567205-C-G

Position:

• chrX-10567205-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.02

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]

ENSG00000291314 (HGNC:):

ACMG classification

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	Protein	UniProt
MID1	NM_000381.4	c.343G>C	p.Glu115Gln	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.343G>C	p.Glu115Gln	missense_variant	2/10	1	NM_000381.4	ENSP00000312678.4
MID1	ENST00000380782.6	c.343G>C	p.Glu115Gln	missense_variant	2/10	1		ENSP00000370159.1
ENSG00000291314	ENST00000706950.1	c.*345G>C		3_prime_UTR_variant	2/2			ENSP00000516670.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD3 exomes AF: 0.00000545 AC: 1 AN: 183349 Hom.: 0 AF XY: 0.0000147 AC XY: 1 AN XY: 67803

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: 1 AN: 1098116 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 1 AN XY: 363472

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.: 22

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	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.22	T;T;T;T;T;T;.;.;T;T;T
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.86	D;.;.;.;.;.;D;D;D;D;D
M_CAP	Pathogenic	0.83	D
MetaRNN	Benign	0.40	T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Uncertain	0.26	D
MutationAssessor	Benign	1.8	L;L;L;L;L;L;L;.;.;.;.
PrimateAI	Uncertain	0.73	T
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	T
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

Other links and lift over

dbSNP: rs104894865; hg19: chrX-10535245;