X-10523193-CAAAAAAAA-CAAAAAAAAAAAAA

Variant names:

• chrX-10523193-C-CAAAAA
• NM_000381.4:c.661-11_661-7dupTTTTT

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS1

The NM_000381.4(MID1):​c.661-11_661-7dupTTTTT 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: not found (cov: 19)
  • Exomes 𝑓: 0.0000027 (0 hom. 0 hem.)
• Consequence: MID1 NM_000381.4 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00

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 Likely_benign. Variant got -4 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.0000027 (2/740961) while in subpopulation AFR AF= 0.000116 (2/17193). AF 95% confidence interval is 0.0000202. There are 0 homozygotes in gnomad4_exome. There are 0 alleles in male gnomad4_exome subpopulation. Median coverage is 0. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MID1	NM_000381.4	c.661-11_661-7dupTTTTT		splice_region_variant, intron_variant	Intron 2 of 9	ENST00000317552.9	NP_000372.1

Ensembl

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

Frequencies

GnomAD3 genomes Cov.: 19

GnomAD4 exome AF: 0.00000270 AC: 2 AN: 740961 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 206253

Gnomad4 AFR exome AF: 0.000116

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 19

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-10491233;