X-10523193-CAAAAAAAA-CAAAAAAA

Position:

• chrX-10523193-CAAAAAAAA-CAAAAAAA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000317552.9(MID1):​c.661-7del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0099 (1 hom., 45 hem., cov: 19)
  • Exomes 𝑓: 0.15 (0 hom. 36 hem.)
• Consequence: MID1 ENST00000317552.9 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter 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 -10 ACMG points.

• BP6: Variant X-10523193-CA-C is Benign according to our data. Variant chrX-10523193-CA-C is described in ClinVar as [Benign]. Clinvar id is 1205954.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-10523193-CA-C is described in Lovd as [Benign]. Variant chrX-10523193-CA-C is described in Lovd as [Benign]. Variant chrX-10523193-CA-C is described in Lovd as [Likely_benign]. Variant chrX-10523193-CA-C is described in Lovd as [Likely_benign].
• BA1: GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.158 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MID1	NM_000381.4	c.661-7del		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.661-7del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_000381.4	ENSP00000312678	P1

Frequencies

GnomAD3 genomes AF: 0.00989 AC: 449 AN: 45385 Hom.: 1 Cov.: 19 AF XY: 0.00501 AC XY: 45 AN XY: 8987

Gnomad AFR AF: 0.0138

Gnomad AMI AF: 0.0512

Gnomad AMR AF: 0.00726

Gnomad ASJ AF: 0.0217

Gnomad EAS AF: 0.00390

Gnomad SAS AF: 0.0124

Gnomad FIN AF: 0.0200

Gnomad MID AF: 0.102

Gnomad NFE AF: 0.00560

Gnomad OTH AF: 0.0105

GnomAD3 exomes AF: 0.207 AC: 9208 AN: 44423 Hom.: 0 AF XY: 0.000712 AC XY: 1 AN XY: 1405

Gnomad AFR exome AF: 0.155

Gnomad AMR exome AF: 0.212

Gnomad ASJ exome AF: 0.180

Gnomad EAS exome AF: 0.211

Gnomad SAS exome AF: 0.173

Gnomad FIN exome AF: 0.171

Gnomad NFE exome AF: 0.227

Gnomad OTH exome AF: 0.225

GnomAD4 exome AF: 0.151 AC: 91779 AN: 606018 Hom.: 0 Cov.: 0 AF XY: 0.000299 AC XY: 36 AN XY: 120394

Gnomad4 AFR exome AF: 0.110

Gnomad4 AMR exome AF: 0.131

Gnomad4 ASJ exome AF: 0.135

Gnomad4 EAS exome AF: 0.140

Gnomad4 SAS exome AF: 0.0930

Gnomad4 FIN exome AF: 0.133

Gnomad4 NFE exome AF: 0.159

Gnomad4 OTH exome AF: 0.151

GnomAD4 genome AF: 0.00989 AC: 449 AN: 45384 Hom.: 1 Cov.: 19 AF XY: 0.00500 AC XY: 45 AN XY: 8996

Gnomad4 AFR AF: 0.0138

Gnomad4 AMR AF: 0.00785

Gnomad4 ASJ AF: 0.0217

Gnomad4 EAS AF: 0.00392

Gnomad4 SAS AF: 0.0124

Gnomad4 FIN AF: 0.0200

Gnomad4 NFE AF: 0.00560

Gnomad4 OTH AF: 0.0104

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:2

Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -
Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -

Computational scores

Source: dbNSFP v4.3

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: rs375668839; hg19: chrX-10491233;