rs534271877

Positions:

• chrX-107917732-G-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_012216.4(MID2):​c.1428G>A​(p.Ala476=) 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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 id 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 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MID2	NM_012216.4	c.1428G>A	p.Ala476=	synonymous_variant	7/10	ENST00000262843.11
LOC101928335	NR_110395.1	n.326+15298C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MID2	ENST00000262843.11	c.1428G>A	p.Ala476=	synonymous_variant	7/10	1	NM_012216.4
	ENST00000663626.2	n.556+15298C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.000178 AC: 20 AN: 112465 Hom.: 1 Cov.: 23 AF XY: 0.000318 AC XY: 11 AN XY: 34619

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

GnomAD3 exomes AF: 0.000760 AC: 139 AN: 182856 Hom.: 1 AF XY: 0.00122 AC XY: 82 AN XY: 67420

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 SAS exome AF: 0.00705

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000331

Gnomad4 SAS exome AF: 0.00779

Gnomad4 FIN exome AF: 0.0000247

Gnomad4 NFE exome AF: 0.0000429

Gnomad4 OTH exome AF: 0.000304

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

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000933

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00590

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000188

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000260 Hom.: 3

Bravo AF: 0.0000227

EpiCase AF: 0.00

EpiControl AF: 0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Apr 27, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	12
DANN	Benign	0.80

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: rs534271877; hg19: chrX-107160962; COSMIC: COSV53311143;