chrX-10567319-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_ModerateBP6BS1BS2

The NM_000381.4(MID1):c.229G>A(p.Val77Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00014 in 1,191,517 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 59 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.000090 ( 0 hom., 3 hem., cov: 22)

Exomes 𝑓: 0.00015 ( 0 hom. 56 hem. )

Consequence

MID1
NM_000381.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 7.75

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 was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.20090812).

BP6

Variant X-10567319-C-T is Benign according to our data. Variant chrX-10567319-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 435864.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Benign=1}. Variant chrX-10567319-C-T is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0000896 (10/111589) while in subpopulation NFE AF = 0.000169 (9/53101). AF 95% confidence interval is 0.0000874. There are 0 homozygotes in GnomAd4. There are 3 alleles in the male GnomAd4 subpopulation. Median coverage is 22. This position FAILED quality control check.

BS2

High Hemizygotes in GnomAd4 at 3 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MID1	NM_000381.4 link	c.229G>A	p.Val77Ile	missense_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.229G>A	p.Val77Ile	missense_variant	Exon 2 of 10	1	NM_000381.4	ENSP00000312678.4	O15344-1
MID1	ENST00000380782.6 link	c.229G>A	p.Val77Ile	missense_variant	Exon 2 of 10	1		ENSP00000370159.1	O15344-2
ENSG00000291314	ENST00000706950.1 link	c.*231G>A		3_prime_UTR_variant	Exon 2 of 2			ENSP00000516670.1	A0A9L9PXS7

Frequencies

GnomAD3 genomes

AF:

0.0000896

AC:

AN:

111589

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.000169

Gnomad OTH

AF:

0.000662

GnomAD2 exomes

AF:

0.000178

AC:

AN:

168386

AF XY:

0.000264

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000304

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000264

Gnomad OTH exome

AF:

0.000242

GnomAD4 exome

AF:

0.000145

AC:

157

AN:

1079928

Hom.:

Cov.:

AF XY:

0.000160

AC XY:

AN XY:

350696

show subpopulations

Gnomad4 AFR exome

AF:

0.0000384

AC:

AN:

26069

Gnomad4 AMR exome

AF:

0.000292

AC:

AN:

34275

Gnomad4 ASJ exome

AF:

0.00

AC:

AN:

18104

Gnomad4 EAS exome

AF:

0.0000667

AC:

AN:

29988

Gnomad4 SAS exome

AF:

0.0000393

AC:

AN:

50933

Gnomad4 FIN exome

AF:

0.00

AC:

AN:

39861

Gnomad4 NFE exome

AF:

0.000158

AC:

131

AN:

831402

Gnomad4 Remaining exome

AF:

0.000177

AC:

AN:

45256

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome 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

GnomAD4 genome

AF:

0.0000896

AC:

AN:

111589

Hom.:

Cov.:

AF XY:

0.0000888

AC XY:

AN XY:

33779

show subpopulations

Gnomad4 AFR

AF:

0.00

AC:

AN:

Gnomad4 AMR

AF:

0.00

AC:

AN:

Gnomad4 ASJ

AF:

0.00

AC:

AN:

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.00

AC:

AN:

Gnomad4 FIN

AF:

0.00

AC:

AN:

Gnomad4 NFE

AF:

0.000169

AC:

0.000169488

AN:

0.000169488

Gnomad4 OTH

AF:

0.000662

AC:

0.000662252

AN:

0.000662252

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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:

0.000302

Hom.:

Bravo

AF:

0.000185

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.000261

AC:

ESP6500EA

AF:

0.000297

AC:

ExAC

AF:

0.000149

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 18, 2016

Genetic Services Laboratory, University of Chicago

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Nov 21, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.46

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.16

T;T;T;T;T;T;.;.;T;T;T

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.97

D;.;.;.;.;.;D;D;D;D;D

M_CAP

Pathogenic

0.38

MetaRNN

Benign

0.20

T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

L;L;L;L;L;L;L;.;.;.;.

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-0.050

N;N;N;N;N;N;N;N;.;.;N

REVEL

Benign

0.16

Sift

Benign

0.053

T;T;T;T;T;T;D;D;.;.;T

Sift4G

Benign

0.51

T;T;T;T;T;T;T;.;T;T;.

Polyphen

0.63

P;P;P;P;P;P;P;D;.;.;B

Vest4

0.22

MVP

0.51

MPC

1.4

ClinPred

0.12

GERP RS

5.6

Varity_R

0.27

gMVP

0.71

Mutation Taster

=63/37

polymorphism

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