rs534271877

Variant names:

• chrX-107917732-G-A
• rs534271877
• NM_012216.4:c.1428G>A

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_012216.4(MID2):​c.1428G>A​(p.Ala476Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000408 in 1,208,044 control chromosomes in the GnomAD database, including 3 homozygotes. There are 292 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00016 (0 hom., 11 hem., cov: 23)
  • Exomes 𝑓: 0.00043 (3 hom. 281 hem.)
• Consequence: MID2 NM_012216.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.23
• Publications: 1 publications found

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]

MID2 Gene-Disease associations (from GenCC):

• non-syndromic X-linked intellectual disability

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet
• intellectual disability, X-linked 101

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ENSG00000236064 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP6: Variant X-107917732-G-A is Benign according to our data. Variant chrX-107917732-G-A is described in ClinVar as Benign. ClinVar VariationId is 435868.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.23 with no splicing effect.
• BS2: High Hemizygotes in GnomAd4 at 11 Unknown,XL gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012216.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MID2	NM_012216.4	MANE Select	c.1428G>A	p.Ala476Ala	synonymous	Exon 7 of 10	NP_036348.2
	MID2	NM_001382751.1		c.1368G>A	p.Ala456Ala	synonymous	Exon 7 of 10	NP_001369680.1
	MID2	NM_052817.3		c.1345+83G>A		intron	N/A	NP_438112.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MID2	ENST00000262843.11	TSL:1 MANE Select	c.1428G>A	p.Ala476Ala	synonymous	Exon 7 of 10	ENSP00000262843.6
	MID2	ENST00000443968.2	TSL:1	c.1345+83G>A		intron	N/A	ENSP00000413976.2
	ENSG00000236064	ENST00000430140.3	TSL:2	n.522+15298C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000178 AC: 20 AN: 112465 Hom.: 1 Cov.: 23

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000934

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00662

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000188

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000760 AC: 139 AN: 182856 AF XY: 0.00122

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000491

Gnomad OTH exome AF: 0.000221

GnomAD4 exome AF: 0.000434 AC: 475 AN: 1095525 Hom.: 3 Cov.: 29 AF XY: 0.000779 AC XY: 281 AN XY: 360949

African (AFR) AF: 0.00 AC: 0 AN: 26345

American (AMR) AF: 0.00 AC: 0 AN: 35187

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19347

East Asian (EAS) AF: 0.0000331 AC: 1 AN: 30181

South Asian (SAS) AF: 0.00779 AC: 421 AN: 54032

European-Finnish (FIN) AF: 0.0000247 AC: 1 AN: 40523

Middle Eastern (MID) AF: 0.000484 AC: 2 AN: 4128

European-Non Finnish (NFE) AF: 0.0000429 AC: 36 AN: 839765

Other (OTH) AF: 0.000304 AC: 14 AN: 46017

GnomAD4 genome AF: 0.000160 AC: 18 AN: 112519 Hom.: 0 Cov.: 23 AF XY: 0.000317 AC XY: 11 AN XY: 34683

African (AFR) AF: 0.00 AC: 0 AN: 31000

American (AMR) AF: 0.0000933 AC: 1 AN: 10716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2652

East Asian (EAS) AF: 0.00 AC: 0 AN: 3586

South Asian (SAS) AF: 0.00590 AC: 16 AN: 2712

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6147

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 217

European-Non Finnish (NFE) AF: 0.0000188 AC: 1 AN: 53278

Other (OTH) AF: 0.00 AC: 0 AN: 1528

Alfa AF: 0.000260 Hom.: 3

Bravo AF: 0.0000227

EpiCase AF: 0.00

EpiControl AF: 0.000237

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	12
DANN	Benign	0.80
PhyloP100		1.2
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: rs534271877; hg19: chrX-107160962; COSMIC: COSV53311143;