Genetic Variant MID1:c.661-10_661-7dupTTTT (chrX-10523193-C-CAAAA) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_000381.4(MID1):c.661-10_661-7dupTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000022 ( 0 hom., 1 hem., cov: 19)

Exomes 𝑓: 0.000047 ( 0 hom. 0 hem. )

Consequence

MID1
NM_000381.4 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.00

Publications

3 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MID1	NM_000381.4 link	c.661-10_661-7dupTTTT		splice_region_variant, intron_variant	Intron 2 of 9	ENST00000317552.9	NP_000372.1	O15344-1A0A024RBV4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MID1	ENST00000317552.9 link	c.661-7_661-6insTTTT		splice_region_variant, intron_variant	Intron 2 of 9	1	NM_000381.4	ENSP00000312678.4		O15344-1
MID1	ENST00000380782.6 link	c.661-7_661-6insTTTT		splice_region_variant, intron_variant	Intron 2 of 9	1		ENSP00000370159.1		O15344-2

Frequencies

GnomAD3 genomes

AF:

0.0000220

AC:

AN:

45445

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000651

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000472

AC:

AN:

740833

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

206175

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.000815

AC:

AN:

17181

American (AMR)

AF:

0.000137

AC:

AN:

21884

Ashkenazi Jewish (ASJ)

AF:

0.0000678

AC:

AN:

14745

East Asian (EAS)

AF:

0.0000401

AC:

AN:

24951

South Asian (SAS)

AF:

0.0000544

AC:

AN:

36735

European-Finnish (FIN)

AF:

0.0000372

AC:

AN:

26856

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2252

European-Non Finnish (NFE)

AF:

0.0000213

AC:

AN:

562683

Other (OTH)

AF:

0.0000298

AC:

AN:

33546

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.315

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

AF:

0.0000220

AC:

AN:

45445

Hom.:

Cov.:

AF XY:

0.000111

AC XY:

AN XY:

9019

show subpopulations

African (AFR)

AF:

0.0000651

AC:

AN:

15351

American (AMR)

AF:

0.00

AC:

AN:

3450

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1063

East Asian (EAS)

AF:

0.00

AC:

AN:

1285

South Asian (SAS)

AF:

0.00

AC:

AN:

972

European-Finnish (FIN)

AF:

0.00

AC:

AN:

1502

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

20938

Other (OTH)

AF:

0.00

AC:

AN:

571

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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X-10523193-CAAAAAAAA-CAAAAAAAAAAAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over