X-107840845-A-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_012216.4(MID2):c.180A>C(p.Ser60=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0698 in 1,209,290 control chromosomes in the GnomAD database, including 2,463 homozygotes. There are 27,770 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.10 (585 hom., 3141 hem., cov: 22)
  • Exomes 𝑓: 0.067 (1878 hom. 24629 hem.)
• Consequence: MID2 NM_012216.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.279

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]

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant X-107840845-A-C is Benign according to our data. Variant chrX-107840845-A-C is described in ClinVar as [Benign]. Clinvar id is 1321169.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.279 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MID2	NM_012216.4	c.180A>C	p.Ser60=	synonymous_variant	2/10	ENST00000262843.11
MID2	NM_001382751.1	c.120A>C	p.Ser40=	synonymous_variant	2/10
MID2	NM_052817.3	c.180A>C	p.Ser60=	synonymous_variant	2/10
MID2	NM_001382752.1	c.120A>C	p.Ser40=	synonymous_variant	2/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MID2	ENST00000262843.11	c.180A>C	p.Ser60=	synonymous_variant	2/10	1	NM_012216.4
MID2	ENST00000443968.2	c.180A>C	p.Ser60=	synonymous_variant	2/10	1		P1
MID2	ENST00000451923.1	c.120A>C	p.Ser40=	synonymous_variant	2/2	3

Frequencies

GnomAD3 genomes AF: 0.100 AC: 11131 AN: 111023 Hom.: 584 Cov.: 22 AF XY: 0.0940 AC XY: 3126 AN XY: 33253

Gnomad AFR AF: 0.192

Gnomad AMI AF: 0.228

Gnomad AMR AF: 0.0624

Gnomad ASJ AF: 0.0436

Gnomad EAS AF: 0.107

Gnomad SAS AF: 0.0949

Gnomad FIN AF: 0.0651

Gnomad MID AF: 0.0917

Gnomad NFE AF: 0.0611

Gnomad OTH AF: 0.0694

GnomAD3 exomes AF: 0.0775 AC: 14208 AN: 183300 Hom.: 448 AF XY: 0.0761 AC XY: 5163 AN XY: 67804

Gnomad AFR exome AF: 0.196

Gnomad AMR exome AF: 0.0556

Gnomad ASJ exome AF: 0.0476

Gnomad EAS exome AF: 0.106

Gnomad SAS exome AF: 0.0894

Gnomad FIN exome AF: 0.0698

Gnomad NFE exome AF: 0.0628

Gnomad OTH exome AF: 0.0704

GnomAD4 exome AF: 0.0668 AC: 73308 AN: 1098216 Hom.: 1878 Cov.: 32 AF XY: 0.0677 AC XY: 24629 AN XY: 363574

Gnomad4 AFR exome AF: 0.200

Gnomad4 AMR exome AF: 0.0548

Gnomad4 ASJ exome AF: 0.0500

Gnomad4 EAS exome AF: 0.108

Gnomad4 SAS exome AF: 0.0891

Gnomad4 FIN exome AF: 0.0696

Gnomad4 NFE exome AF: 0.0595

Gnomad4 OTH exome AF: 0.0793

GnomAD4 genome AF: 0.100 AC: 11149 AN: 111074 Hom.: 585 Cov.: 22 AF XY: 0.0943 AC XY: 3141 AN XY: 33314

Gnomad4 AFR AF: 0.192

Gnomad4 AMR AF: 0.0628

Gnomad4 ASJ AF: 0.0436

Gnomad4 EAS AF: 0.107

Gnomad4 SAS AF: 0.0968

Gnomad4 FIN AF: 0.0651

Gnomad4 NFE AF: 0.0612

Gnomad4 OTH AF: 0.0685

Alfa AF: 0.0717 Hom.: 2441

Bravo AF: 0.106

EpiCase AF: 0.0635

EpiControl AF: 0.0675

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Intellectual disability, X-linked 101 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
Cadd	Benign	0.55
Dann	Benign	0.64

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: rs2236083; hg19: chrX-107084075; COSMIC: COSV53307754;