rs758037994

Variant names:

• chrX-107915993-CT-C
• rs758037994
• NM_012216.4:c.1074-4delT

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP6_Very_Strong BS2

The NM_012216.4(MID2):​c.1074-4delT variant causes a splice region, intron change. The variant allele was found at a frequency of 0.00239 in 1,199,732 control chromosomes in the GnomAD database, including 4 homozygotes. There are 921 hemizygotes in GnomAD. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0018 (1 hom., 60 hem., cov: 23)
  • Exomes 𝑓: 0.0024 (3 hom. 861 hem.)
• Consequence: MID2 NM_012216.4 splice_region, intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 3.64

Genes affected

MID2 (HGNC:7096): (midline 2) The protein encoded by this gene is a member of the tripartite motif (TRIM) family. 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. The protein localizes to microtubular structures in the cytoplasm. Alternate splicing of this gene results in two transcript variants encoding different isoforms. [provided by RefSeq, Feb 2009]

ENSG00000236064 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP6: Variant X-107915993-CT-C is Benign according to our data. Variant chrX-107915993-CT-C is described in ClinVar as [Likely_benign]. Clinvar id is 445463.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Hemizygotes in GnomAd4 at 60 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MID2	NM_012216.4	c.1074-4delT		splice_region_variant, intron_variant	Intron 5 of 9	ENST00000262843.11	NP_036348.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MID2	ENST00000262843.11	c.1074-8delT		splice_region_variant, intron_variant	Intron 5 of 9	1	NM_012216.4	ENSP00000262843.6

Frequencies

GnomAD3 genomes AF: 0.00183 AC: 204 AN: 111777 Hom.: 1 Cov.: 23

Gnomad AFR AF: 0.000423

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000850

Gnomad ASJ AF: 0.000753

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00518

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00281

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00224 AC: 380 AN: 169336 AF XY: 0.00198

Gnomad AFR exome AF: 0.000318

Gnomad AMR exome AF: 0.00155

Gnomad ASJ exome AF: 0.000571

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00571

Gnomad NFE exome AF: 0.00311

Gnomad OTH exome AF: 0.00121

GnomAD4 exome AF: 0.00245 AC: 2663 AN: 1087904 Hom.: 3 Cov.: 28 AF XY: 0.00242 AC XY: 861 AN XY: 355736

Gnomad4 AFR exome AF: 0.000272 AC: 7 AN: 25757

Gnomad4 AMR exome AF: 0.00143 AC: 47 AN: 32960

Gnomad4 ASJ exome AF: 0.000680 AC: 13 AN: 19109

Gnomad4 EAS exome AF: 0.0000336 AC: 1 AN: 29797

Gnomad4 SAS exome AF: 0.0000578 AC: 3 AN: 51912

Gnomad4 FIN exome AF: 0.00475 AC: 191 AN: 40178

Gnomad4 NFE exome AF: 0.00273 AC: 2289 AN: 838458

Gnomad4 Remaining exome AF: 0.00241 AC: 110 AN: 45636

GnomAD4 genome AF: 0.00182 AC: 204 AN: 111828 Hom.: 1 Cov.: 23 AF XY: 0.00176 AC XY: 60 AN XY: 34046

Gnomad4 AFR AF: 0.000422 AC: 0.00042164 AN: 0.00042164

Gnomad4 AMR AF: 0.000849 AC: 0.000848977 AN: 0.000848977

Gnomad4 ASJ AF: 0.000753 AC: 0.000753296 AN: 0.000753296

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.00 AC: 0 AN: 0

Gnomad4 FIN AF: 0.00518 AC: 0.00517529 AN: 0.00517529

Gnomad4 NFE AF: 0.00281 AC: 0.00280655 AN: 0.00280655

Gnomad4 OTH AF: 0.00 AC: 0 AN: 0

Alfa AF: 0.00262 Hom.: 24

Bravo AF: 0.00153

Asia WGS AF: 0.000400 AC: 1 AN: 2512

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Apr 20, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

Sep 24, 2019

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs758037994; hg19: chrX-107159223;