rs111428432

Variant names:

• chrX-10501436-C-G
• rs111428432
• ENST00000616003.5:c.880G>C

Your query was ambiguous. Multiple possible variants found:

• chrX-10501436-C-G
• chrX-10501436-C-T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS1

The ENST00000616003.5(MID1):​c.880G>C​(p.Glu294Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000347 in 1,153,667 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 9/10 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E294K) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0000090 (0 hom., 1 hem., cov: 23)
  • Exomes 𝑓: 0.0000029 (0 hom. 1 hem.)
• Consequence: MID1 ENST00000616003.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.61
• Publications: 4 publications found

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

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.04762867).
• BS1: Variant frequency is greater than expected in population eas. GnomAdExome4 allele frequency = 0.00000288 (3/1042057) while in subpopulation EAS AF = 0.000111 (3/27131). AF 95% confidence interval is 0.0000293. There are 0 homozygotes in GnomAdExome4. There are 1 alleles in the male GnomAdExome4 subpopulation. Median coverage is 29. This position passed quality control check.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MID1	NM_000381.4	c.757-5745G>C		intron_variant	Intron 3 of 9	ENST00000317552.9	NP_000372.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MID1	ENST00000317552.9	c.757-5745G>C		intron_variant	Intron 3 of 9	1	NM_000381.4	ENSP00000312678.4
MID1	ENST00000380782.6	c.757-5745G>C		intron_variant	Intron 3 of 9	1		ENSP00000370159.1

Frequencies

GnomAD3 genomes AF: 0.00000896 AC: 1 AN: 111610 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000282

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

GnomAD2 exomes AF: 0.0000307 AC: 3 AN: 97874 AF XY: 0.0000273

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000383

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000288 AC: 3 AN: 1042057 Hom.: 0 Cov.: 29 AF XY: 0.00000293 AC XY: 1 AN XY: 341093

African (AFR) AF: 0.00 AC: 0 AN: 24912

American (AMR) AF: 0.00 AC: 0 AN: 27908

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18642

East Asian (EAS) AF: 0.000111 AC: 3 AN: 27131

South Asian (SAS) AF: 0.00 AC: 0 AN: 49872

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 25904

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4087

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 819297

Other (OTH) AF: 0.00 AC: 0 AN: 44304

GnomAD4 genome AF: 0.00000896 AC: 1 AN: 111610 Hom.: 0 Cov.: 23 AF XY: 0.0000296 AC XY: 1 AN XY: 33768

African (AFR) AF: 0.00 AC: 0 AN: 30718

American (AMR) AF: 0.00 AC: 0 AN: 10515

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2637

East Asian (EAS) AF: 0.000282 AC: 1 AN: 3546

South Asian (SAS) AF: 0.00 AC: 0 AN: 2653

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5985

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 237

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53146

Other (OTH) AF: 0.00 AC: 0 AN: 1493

Alfa AF: 0.00 Hom.: 52

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.14
DANN	Benign	0.45
DEOGEN2	Benign	0.011	T
FATHMM_MKL	Benign	0.016	N
LIST_S2	Benign	0.29	T
MetaRNN	Benign	0.048	T
PhyloP100		-1.6
Sift4G	Benign	0.22	T
Vest4		0.097
MVP		0.082
GERP RS		-4.1
Mutation Taster		=100/0	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

Other links and lift over

dbSNP: rs111428432; hg19: chrX-10469476;