Variant X-10523193-CAAAAAAAA-CAAAAAAAAA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The ENST00000317552.9(MID1):c.661-7_661-6insT 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 0.082 ( 127 hom., 533 hem., cov: 19)

Exomes 𝑓: 0.099 ( 7 hom. 96 hem. )

Consequence

MID1
ENST00000317552.9 splice_region, splice_polypyrimidine_tract, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.00

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant X-10523193-C-CA is Benign according to our data. Variant chrX-10523193-C-CA is described in ClinVar as [Benign]. Clinvar id is 196261.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.165 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MID1	NM_000381.4 linkuse as main transcript	c.661-7_661-6insT		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 linkuse as main transcript	c.661-7_661-6insT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_000381.4	ENSP00000312678	P1	O15344-1

Frequencies

GnomAD3 genomes

AF:

0.0820

AC:

3713

AN:

45300

Hom.:

127

Cov.:

AF XY:

0.0592

AC XY:

531

AN XY:

8970

show subpopulations

Gnomad AFR

AF:

0.171

Gnomad AMI

AF:

0.00394

Gnomad AMR

AF:

0.0437

Gnomad ASJ

AF:

0.0405

Gnomad EAS

AF:

0.0101

Gnomad SAS

AF:

0.0556

Gnomad FIN

AF:

0.0810

Gnomad MID

AF:

0.0508

Gnomad NFE

AF:

0.0321

Gnomad OTH

AF:

0.0776

GnomAD3 exomes

AF:

0.138

AC:

6132

AN:

44423

Hom.:

AF XY:

0.0135

AC XY:

AN XY:

1405

show subpopulations

Gnomad AFR exome

AF:

0.188

Gnomad AMR exome

AF:

0.129

Gnomad ASJ exome

AF:

0.153

Gnomad EAS exome

AF:

0.166

Gnomad SAS exome

AF:

0.150

Gnomad FIN exome

AF:

0.105

Gnomad NFE exome

AF:

0.128

Gnomad OTH exome

AF:

0.133

GnomAD4 exome

AF:

0.0987

AC:

65056

AN:

659239

Hom.:

Cov.:

AF XY:

0.000648

AC XY:

AN XY:

148087

show subpopulations

Gnomad4 AFR exome

AF:

0.147

Gnomad4 AMR exome

AF:

0.0819

Gnomad4 ASJ exome

AF:

0.0956

Gnomad4 EAS exome

AF:

0.0889

Gnomad4 SAS exome

AF:

0.0681

Gnomad4 FIN exome

AF:

0.104

Gnomad4 NFE exome

AF:

0.0998

Gnomad4 OTH exome

AF:

0.101

GnomAD4 genome

AF:

0.0820

AC:

3716

AN:

45299

Hom.:

127

Cov.:

AF XY:

0.0594

AC XY:

533

AN XY:

8979

show subpopulations

Gnomad4 AFR

AF:

0.171

Gnomad4 AMR

AF:

0.0437

Gnomad4 ASJ

AF:

0.0405

Gnomad4 EAS

AF:

0.0102

Gnomad4 SAS

AF:

0.0571

Gnomad4 FIN

AF:

0.0810

Gnomad4 NFE

AF:

0.0321

Gnomad4 OTH

AF:

0.0768

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Nov 30, 2014	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -

not provided

Benign:2

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

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over