chrX-107840906-T-A

Position:

• chrX-107840906-T-A

Variant summary

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

The NM_012216.4(MID2):​c.241T>A​(p.Tyr81Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000182 in 1,097,984 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: 0.0000018 (0 hom. 0 hem.)
• Consequence: MID2 NM_012216.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.15

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=0.37860218).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MID2	NM_012216.4	c.241T>A	p.Tyr81Asn	missense_variant	2/10	ENST00000262843.11	NP_036348.2
MID2	NM_001382751.1	c.181T>A	p.Tyr61Asn	missense_variant	2/10		NP_001369680.1
MID2	NM_052817.3	c.241T>A	p.Tyr81Asn	missense_variant	2/10		NP_438112.2
MID2	NM_001382752.1	c.181T>A	p.Tyr61Asn	missense_variant	2/10		NP_001369681.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MID2	ENST00000262843.11	c.241T>A	p.Tyr81Asn	missense_variant	2/10	1	NM_012216.4	ENSP00000262843.6
MID2	ENST00000443968.2	c.241T>A	p.Tyr81Asn	missense_variant	2/10	1		ENSP00000413976.2
MID2	ENST00000451923.1	c.181T>A	p.Tyr61Asn	missense_variant	2/2	3		ENSP00000410730.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.00000182 AC: 2 AN: 1097984 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 363340

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000662

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

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 29, 2024

The c.241T>A (p.Y81N) alteration is located in exon 2 (coding exon 2) of the MID2 gene. This alteration results from a T to A substitution at nucleotide position 241, causing the tyrosine (Y) at amino acid position 81 to be replaced by an asparagine (N). 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	0.48
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.070
CADD	Uncertain	24
DANN	Benign	0.96
DEOGEN2	Benign	0.023	T;T;.
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.97	D;D;D
M_CAP	Uncertain	0.15	D
MetaRNN	Benign	0.38	T;T;T
MetaSVM	Benign	-0.50	T
MutationAssessor	Benign	-0.27	.;N;N
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	-0.94	N;N;N
REVEL	Uncertain	0.46
Sift	Uncertain	0.0090	D;D;D
Sift4G	Benign	0.50	T;T;T
Polyphen		0.87, 0.095	.;P;B
Vest4		0.76, 0.71
MutPred		0.44		.;Gain of relative solvent accessibility (P = 0.1571);Gain of relative solvent accessibility (P = 0.1571);
MVP		0.95
MPC		1.5
ClinPred		0.86	D
GERP RS		4.8
Varity_R		0.54
gMVP		0.58

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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-107084136;