X-107841021-A-G

Position:

• chrX-107841021-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_012216.4(MID2):​c.356A>G​(p.Glu119Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000911 in 1,098,090 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 9.1e-7 (0 hom. 0 hem.)
• Consequence: MID2 NM_012216.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.57

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29361635).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MID2	NM_012216.4	c.356A>G	p.Glu119Gly	missense_variant	2/10	ENST00000262843.11	NP_036348.2
MID2	NM_001382751.1	c.296A>G	p.Glu99Gly	missense_variant	2/10		NP_001369680.1
MID2	NM_052817.3	c.356A>G	p.Glu119Gly	missense_variant	2/10		NP_438112.2
MID2	NM_001382752.1	c.296A>G	p.Glu99Gly	missense_variant	2/10		NP_001369681.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MID2	ENST00000262843.11	c.356A>G	p.Glu119Gly	missense_variant	2/10	1	NM_012216.4	ENSP00000262843.6
MID2	ENST00000443968.2	c.356A>G	p.Glu119Gly	missense_variant	2/10	1		ENSP00000413976.2
MID2	ENST00000451923.1	c.296A>G	p.Glu99Gly	missense_variant	2/2	3		ENSP00000410730.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 9.11e-7 AC: 1 AN: 1098090 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 363446

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000119

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 28, 2024

The c.356A>G (p.E119G) alteration is located in exon 2 (coding exon 2) of the MID2 gene. This alteration results from a A to G substitution at nucleotide position 356, causing the glutamic acid (E) at amino acid position 119 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Benign	-0.052	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.023	T;T;.
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.94	D;D;D
M_CAP	Pathogenic	0.43	D
MetaRNN	Benign	0.29	T;T;T
MetaSVM	Benign	-0.43	T
MutationAssessor	Uncertain	2.7	.;M;M
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-2.3	N;N;N
REVEL	Benign	0.23
Sift	Uncertain	0.0030	D;D;D
Sift4G	Benign	0.22	T;D;D
Polyphen		0.92, 0.91	.;P;P
Vest4		0.21, 0.26
MutPred		0.17		.;Gain of glycosylation at S118 (P = 0.0273);Gain of glycosylation at S118 (P = 0.0273);
MVP		0.57
MPC		0.88
ClinPred		0.94	D
GERP RS		5.9
Varity_R		0.48
gMVP		0.56

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-107084251;