rs140708189

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_000381.4(MID1):c.75C>T(p.Cys25Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00307 in 1,209,695 control chromosomes in the GnomAD database, including 11 homozygotes. There are 1,166 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0022 ( 1 hom., 82 hem., cov: 22)

Exomes 𝑓: 0.0032 ( 10 hom. 1084 hem. )

Consequence

MID1
NM_000381.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.797

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:

ENSG00000291314 (HGNC:):

ENSG00000291314 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant X-10567473-G-A is Benign according to our data. Variant chrX-10567473-G-A is described in ClinVar as [Benign]. Clinvar id is 129612.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-10567473-G-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-0.797 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00216 (241/111646) while in subpopulation SAS AF= 0.00384 (10/2607). AF 95% confidence interval is 0.0029. There are 1 homozygotes in gnomad4. There are 82 alleles in male gnomad4 subpopulation. Median coverage is 22. This position pass quality control queck.

BS2

High Hemizygotes in GnomAd4 at 82 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MID1	NM_000381.4 link	c.75C>T	p.Cys25Cys	synonymous_variant	Exon 2 of 10	ENST00000317552.9	NP_000372.1	O15344-1A0A024RBV4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MID1	ENST00000317552.9 link	c.75C>T	p.Cys25Cys	synonymous_variant	Exon 2 of 10	1	NM_000381.4	ENSP00000312678.4	O15344-1
MID1	ENST00000380782.6 link	c.75C>T	p.Cys25Cys	synonymous_variant	Exon 2 of 10	1		ENSP00000370159.1	O15344-2
ENSG00000291314	ENST00000706950.1 link	c.*77C>T		3_prime_UTR_variant	Exon 2 of 2			ENSP00000516670.1	A0A9L9PXS7

Frequencies

GnomAD3 genomes

AF:

0.00215

AC:

240

AN:

111593

Hom.:

Cov.:

AF XY:

0.00240

AC XY:

AN XY:

33783

show subpopulations

Gnomad AFR

AF:

0.000457

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000377

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000283

Gnomad SAS

AF:

0.00344

Gnomad FIN

AF:

0.00482

Gnomad MID

AF:

0.00837

Gnomad NFE

AF:

0.00330

Gnomad OTH

AF:

0.00398

GnomAD3 exomes

AF:

0.00272

AC:

497

AN:

182791

Hom.:

AF XY:

0.00254

AC XY:

171

AN XY:

67393

show subpopulations

Gnomad AFR exome

AF:

0.000532

Gnomad AMR exome

AF:

0.000547

Gnomad ASJ exome

AF:

0.000134

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00289

Gnomad FIN exome

AF:

0.00619

Gnomad NFE exome

AF:

0.00378

Gnomad OTH exome

AF:

0.00288

GnomAD4 exome

AF:

0.00317

AC:

3477

AN:

1098049

Hom.:

Cov.:

AF XY:

0.00298

AC XY:

1084

AN XY:

363403

show subpopulations

Gnomad4 AFR exome

AF:

0.000341

Gnomad4 AMR exome

AF:

0.000596

Gnomad4 ASJ exome

AF:

0.0000516

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00305

Gnomad4 FIN exome

AF:

0.00639

Gnomad4 NFE exome

AF:

0.00338

Gnomad4 OTH exome

AF:

0.00330

GnomAD4 genome

AF:

0.00216

AC:

241

AN:

111646

Hom.:

Cov.:

AF XY:

0.00242

AC XY:

AN XY:

33846

show subpopulations

Gnomad4 AFR

AF:

0.000456

Gnomad4 AMR

AF:

0.000377

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000284

Gnomad4 SAS

AF:

0.00384

Gnomad4 FIN

AF:

0.00482

Gnomad4 NFE

AF:

0.00330

Gnomad4 OTH

AF:

0.00393

Alfa

AF:

0.00294

Hom.:

Bravo

AF:

0.00164

EpiCase

AF:

0.00354

EpiControl

AF:

0.00296

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Dec 28, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified

Benign:1

Mar 17, 2014

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Inborn genetic diseases

Benign:1

Jun 23, 2017

Ambry Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

1.3

DANN

Benign

0.54

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