Variant chrX-10523193-CAA-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_StrongBS1

The ENST00000317552.9(MID1):c.661-8_661-7del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0229 in 711,540 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00033 ( 0 hom., 0 hem., cov: 19)

Exomes 𝑓: 0.024 ( 0 hom. 0 hem. )

Consequence

MID1
ENST00000317552.9 splice_region, splice_polypyrimidine_tract, intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP6

Variant X-10523193-CAA-C is Benign according to our data. Variant chrX-10523193-CAA-C is described in ClinVar as [Likely_benign]. Clinvar id is 211500.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00033 (15/45394) while in subpopulation NFE AF= 0.000335 (7/20924). AF 95% confidence interval is 0.000156. There are 0 homozygotes in gnomad4. There are 0 alleles in male gnomad4 subpopulation. Median coverage is 19. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MID1	NM_000381.4 linkuse as main transcript	c.661-8_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 linkuse as main transcript	c.661-8_661-7del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_000381.4	ENSP00000312678	P1	O15344-1

Frequencies

GnomAD3 genomes

AF:

0.000330

AC:

AN:

45394

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

9008

show subpopulations

Gnomad AFR

AF:

0.0000652

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00189

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00338

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000335

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0311

AC:

1382

AN:

44423

Hom.:

AF XY:

0.00

AC XY:

AN XY:

1405

show subpopulations

Gnomad AFR exome

AF:

0.0177

Gnomad AMR exome

AF:

0.0485

Gnomad ASJ exome

AF:

0.0267

Gnomad EAS exome

AF:

0.0398

Gnomad SAS exome

AF:

0.0255

Gnomad FIN exome

AF:

0.0256

Gnomad NFE exome

AF:

0.0272

Gnomad OTH exome

AF:

0.0400

GnomAD4 exome

AF:

0.0244

AC:

16251

AN:

666146

Hom.:

AF XY:

0.00

AC XY:

AN XY:

174846

show subpopulations

Gnomad4 AFR exome

AF:

0.0183

Gnomad4 AMR exome

AF:

0.0230

Gnomad4 ASJ exome

AF:

0.0206

Gnomad4 EAS exome

AF:

0.0168

Gnomad4 SAS exome

AF:

0.0127

Gnomad4 FIN exome

AF:

0.0158

Gnomad4 NFE exome

AF:

0.0264

Gnomad4 OTH exome

AF:

0.0222

GnomAD4 genome

AF:

0.000330

AC:

AN:

45394

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

9008

show subpopulations

Gnomad4 AFR

AF:

0.0000652

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00189

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00338

Gnomad4 NFE

AF:

0.000335

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Jul 21, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Oct 30, 2015	- -

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