rs10521612

Variant names:

• chrX-10617481-G-A
• rs10521612
• NM_000381.4:c.-57+2809C>T

Your query was ambiguous. Multiple possible variants found:

• chrX-10617481-G-A
• chrX-10617481-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000381.4(MID1):​c.-57+2809C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0459 in 112,225 control chromosomes in the GnomAD database, including 199 homozygotes. There are 1,454 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.046 (199 hom., 1454 hem., cov: 24)
• Consequence: MID1 NM_000381.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.47
• Publications: 0 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.119 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MID1	NM_000381.4	c.-57+2809C>T		intron_variant	Intron 1 of 9	ENST00000317552.9	NP_000372.1
MID1	NM_001098624.2	c.-56-49878C>T		intron_variant	Intron 1 of 9		NP_001092094.1
MID1	NM_033290.4	c.-56-49878C>T		intron_variant	Intron 1 of 9		NP_150632.1
MID1	NM_033289.2	c.-57+2809C>T		intron_variant	Intron 1 of 9		NP_150631.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MID1	ENST00000317552.9	c.-57+2809C>T		intron_variant	Intron 1 of 9	1	NM_000381.4	ENSP00000312678.4
MID1	ENST00000380782.6	c.-57+2809C>T		intron_variant	Intron 1 of 9	1		ENSP00000370159.1

Frequencies

GnomAD3 genomes AF: 0.0459 AC: 5148 AN: 112170 Hom.: 199 Cov.: 24

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.0160

Gnomad AMR AF: 0.0318

Gnomad ASJ AF: 0.00905

Gnomad EAS AF: 0.00111

Gnomad SAS AF: 0.0126

Gnomad FIN AF: 0.0145

Gnomad MID AF: 0.0252

Gnomad NFE AF: 0.0147

Gnomad OTH AF: 0.0536

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0459 AC: 5151 AN: 112225 Hom.: 199 Cov.: 24 AF XY: 0.0423 AC XY: 1454 AN XY: 34401

African (AFR) AF: 0.123 AC: 3783 AN: 30849

American (AMR) AF: 0.0317 AC: 336 AN: 10614

Ashkenazi Jewish (ASJ) AF: 0.00905 AC: 24 AN: 2653

East Asian (EAS) AF: 0.00111 AC: 4 AN: 3595

South Asian (SAS) AF: 0.0127 AC: 34 AN: 2685

European-Finnish (FIN) AF: 0.0145 AC: 89 AN: 6120

Middle Eastern (MID) AF: 0.0276 AC: 6 AN: 217

European-Non Finnish (NFE) AF: 0.0147 AC: 783 AN: 53274

Other (OTH) AF: 0.0529 AC: 81 AN: 1530

Alfa AF: 0.0269 Hom.: 1082

Bravo AF: 0.0516

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	12
DANN	Benign	0.62
PhyloP100		1.5
Mutation Taster		=100/0	polymorphism (auto)

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: rs10521612; hg19: chrX-10585521;