rs10521612

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
MID1	NM_000381.4	c.-57+2809C>T		intron_variant		ENST00000317552.9	NP_000372.1
MID1	NM_001098624.2	c.-56-49878C>T		intron_variant			NP_001092094.1
MID1	NM_033289.2	c.-57+2809C>T		intron_variant			NP_150631.1
MID1	NM_033290.4	c.-56-49878C>T		intron_variant			NP_150632.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MID1	ENST00000317552.9	c.-57+2809C>T		intron_variant		1	NM_000381.4	ENSP00000312678	P1

Frequencies

GnomAD3 genomes AF: 0.0459 AC: 5148 AN: 112170 Hom.: 199 Cov.: 24 AF XY: 0.0423 AC XY: 1452 AN XY: 34336

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

Gnomad4 AFR AF: 0.123

Gnomad4 AMR AF: 0.0317

Gnomad4 ASJ AF: 0.00905

Gnomad4 EAS AF: 0.00111

Gnomad4 SAS AF: 0.0127

Gnomad4 FIN AF: 0.0145

Gnomad4 NFE AF: 0.0147

Gnomad4 OTH AF: 0.0529

Alfa AF: 0.0214 Hom.: 610

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

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

Other links and lift over

dbSNP: rs10521612; hg19: chrX-10585521;