rs140708189

Variant names:

Variant summary

Our verdict is Benign. The variant received -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

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

X-linked Opitz G/BBB syndrome
Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: ClinGen, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics

MID1 links:

ENSG00000291314 (HGNC:):

ENSG00000291314 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 129612.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 the male GnomAd4 subpopulation. Median coverage is 22. This position passed quality control check.

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

Ensembl

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

Frequencies

GnomAD3 genomes

AF:

0.00215

AC:

240

AN:

111593

Hom.:

Cov.:

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

GnomAD2 exomes

AF:

0.00272

AC:

497

AN:

182791

AF XY:

0.00254

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 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

African (AFR)

AF:

0.000341

AC:

AN:

26399

American (AMR)

AF:

0.000596

AC:

AN:

35207

Ashkenazi Jewish (ASJ)

AF:

0.0000516

AC:

AN:

19383

East Asian (EAS)

AF:

0.00

AC:

AN:

30205

South Asian (SAS)

AF:

0.00305

AC:

165

AN:

54137

European-Finnish (FIN)

AF:

0.00639

AC:

259

AN:

40526

Middle Eastern (MID)

AF:

0.00580

AC:

AN:

4137

European-Non Finnish (NFE)

AF:

0.00338

AC:

2846

AN:

841963

Other (OTH)

AF:

0.00330

AC:

152

AN:

46092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

154

307

461

614

768

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

200

300

400

500

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00216

AC:

241

AN:

111646

Hom.:

Cov.:

AF XY:

0.00242

AC XY:

AN XY:

33846

show subpopulations

African (AFR)

AF:

0.000456

AC:

AN:

30700

American (AMR)

AF:

0.000377

AC:

AN:

10619

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2650

East Asian (EAS)

AF:

0.000284

AC:

AN:

3518

South Asian (SAS)

AF:

0.00384

AC:

AN:

2607

European-Finnish (FIN)

AF:

0.00482

AC:

AN:

6022

Middle Eastern (MID)

AF:

0.00917

AC:

AN:

218

European-Non Finnish (NFE)

AF:

0.00330

AC:

175

AN:

53099

Other (OTH)

AF:

0.00393

AC:

AN:

1528

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Dec 28, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

(source)

DANN

Benign

0.54

PhyloP100

-0.80

PromoterAI

-0.041

Neutral

(source)

Mutation Taster

=89/11

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over