chrX-10523193-C-CAA

Position:

• chrX-10523193-C-CAA

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The ENST00000317552.9(MID1):​c.661-7_661-6insTT variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.060 (140 hom., 344 hem., cov: 19)
  • Exomes 𝑓: 0.0042 (0 hom. 25 hem.)
• Consequence: MID1 ENST00000317552.9 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.00

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]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant X-10523193-C-CAA is Benign according to our data. Variant chrX-10523193-C-CAA is described in ClinVar as [Benign]. Clinvar id is 196260.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.164 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MID1	NM_000381.4	c.661-7_661-6insTT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000317552.9	NP_000372.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MID1	ENST00000317552.9	c.661-7_661-6insTT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_000381.4	ENSP00000312678	P1

Frequencies

GnomAD3 genomes AF: 0.0603 AC: 2734 AN: 45374 Hom.: 140 Cov.: 19 AF XY: 0.0382 AC XY: 344 AN XY: 9002

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0299

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000666

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000669

Gnomad OTH AF: 0.0473

GnomAD3 exomes AF: 0.0154 AC: 682 AN: 44423 Hom.: 2 AF XY: 0.00427 AC XY: 6 AN XY: 1405

Gnomad AFR exome AF: 0.0785

Gnomad AMR exome AF: 0.0118

Gnomad ASJ exome AF: 0.0124

Gnomad EAS exome AF: 0.00712

Gnomad SAS exome AF: 0.0111

Gnomad FIN exome AF: 0.00788

Gnomad NFE exome AF: 0.00773

Gnomad OTH exome AF: 0.0139

GnomAD4 exome AF: 0.00419 AC: 3058 AN: 730559 Hom.: 0 Cov.: 0 AF XY: 0.000124 AC XY: 25 AN XY: 200851

Gnomad4 AFR exome AF: 0.0584

Gnomad4 AMR exome AF: 0.00552

Gnomad4 ASJ exome AF: 0.00357

Gnomad4 EAS exome AF: 0.000771

Gnomad4 SAS exome AF: 0.00237

Gnomad4 FIN exome AF: 0.00246

Gnomad4 NFE exome AF: 0.00277

Gnomad4 OTH exome AF: 0.00667

GnomAD4 genome AF: 0.0603 AC: 2735 AN: 45373 Hom.: 140 Cov.: 19 AF XY: 0.0382 AC XY: 344 AN XY: 9011

Gnomad4 AFR AF: 0.169

Gnomad4 AMR AF: 0.0299

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000666

Gnomad4 NFE AF: 0.000669

Gnomad4 OTH AF: 0.0468

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Nov 25, 2014	- -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Mar 01, 2021	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Jun 12, 2015	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs375668839; hg19: chrX-10491233;