rs587777605

chrX-107905593-G-A

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP5 BS2

The NM_012216.4(MID2):c.1040G>A(p.Arg347Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000147 in 1,088,323 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 10 hemizygotes in GnomAD. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.000015 (0 hom. 10 hem.)
• Consequence: MID2 NM_012216.4 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 7.68

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 Likely_benign. Variant got -3 ACMG points.

• PP5: Variant X-107905593-G-A is Pathogenic according to our data. Variant chrX-107905593-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 143857.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-107905593-G-A is described in Lovd as [Likely_pathogenic].
• BS2: High Hemizygotes in GnomAdExome at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MID2	NM_012216.4	c.1040G>A	p.Arg347Gln	missense_variant	5/10	ENST00000262843.11
LOC101928335	NR_110395.1	n.327-9233C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MID2	ENST00000262843.11	c.1040G>A	p.Arg347Gln	missense_variant	5/10	1	NM_012216.4
	ENST00000663626.2	n.556+27437C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD3 exomes AF: 0.0000171 AC: 3 AN: 175099 Hom.: 0 AF XY: 0.0000332 AC XY: 2 AN XY: 60321

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: 0.000179

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000147 AC: 16 AN: 1088323 Hom.: 0 Cov.: 28 AF XY: 0.0000282 AC XY: 10 AN XY: 354551

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000292

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 23

ExAC AF: 0.0000330 AC: 4

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Intellectual disability, X-linked 101 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jan 01, 2014

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.079	T
BayesDel_noAF	Uncertain	-0.080
Cadd	Uncertain	23
Dann	Pathogenic	1.0
DEOGEN2	Benign	0.056	T;.
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	1.0	D;D
M_CAP	Pathogenic	0.55	D
MetaRNN	Uncertain	0.43	T;T
MetaSVM	Benign	-0.53	T
MutationAssessor	Uncertain	2.2	M;M
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-1.1	N;N
REVEL	Benign	0.21
Sift	Benign	0.10	T;T
Sift4G	Benign	0.27	T;T
Polyphen		1.0	D;P
Vest4		0.26
MutPred		0.57		Loss of helix (P = 0.0376);Loss of helix (P = 0.0376);
MVP		0.72
MPC		0.97
ClinPred		0.53	D
GERP RS		5.5
Varity_R		0.32
gMVP		0.60

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: rs587777605; hg19: chrX-107148823;