11-118260093-C-A

Variant names:

• chr11-118260093-C-A
• NM_005797.4:c.545G>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_005797.4(MPZL2):​c.545G>T​(p.Arg182Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,772 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: MPZL2 NM_005797.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.608

Genes affected

MPZL2 (HGNC:3496): (myelin protein zero like 2) Thymus development depends on a complex series of interactions between thymocytes and the stromal component of the organ. Epithelial V-like antigen (EVA) is expressed in thymus epithelium and strongly downregulated by thymocyte developmental progression. This gene is expressed in the thymus and in several epithelial structures early in embryogenesis. It is highly homologous to the myelin protein zero and, in thymus-derived epithelial cell lines, is poorly soluble in nonionic detergents, strongly suggesting an association to the cytoskeleton. Its capacity to mediate cell adhesion through a homophilic interaction and its selective regulation by T cell maturation might imply the participation of EVA in the earliest phases of thymus organogenesis. The protein bears a characteristic V-type domain and two potential N-glycosylation sites in the extracellular domain; a putative serine phosphorylation site for casein kinase 2 is also present in the cytoplasmic tail. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MPZL2	NM_005797.4	c.545G>T	p.Arg182Leu	missense_variant	Exon 4 of 6	ENST00000278937.7	NP_005788.1
MPZL2	NM_144765.3	c.545G>T	p.Arg182Leu	missense_variant	Exon 4 of 5		NP_658911.1
MPZL2	XM_047426229.1	c.*52G>T		3_prime_UTR_variant	Exon 4 of 4		XP_047282185.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MPZL2	ENST00000278937.7	c.545G>T	p.Arg182Leu	missense_variant	Exon 4 of 6	1	NM_005797.4	ENSP00000278937.2
MPZL2	ENST00000438295.2	c.545G>T	p.Arg182Leu	missense_variant	Exon 4 of 5	1		ENSP00000408362.2
MPZL2	ENST00000529376.5	n.675G>T		non_coding_transcript_exon_variant	Exon 4 of 4	2
MPZL2	ENST00000534175.6	n.593G>T		non_coding_transcript_exon_variant	Exon 3 of 5	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461772 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727180

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.41	T;T
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.79	.;T
M_CAP	Uncertain	0.094	D
MetaRNN	Uncertain	0.46	T;T
MetaSVM	Uncertain	0.67	D
MutationAssessor	Uncertain	2.5	M;M
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-2.5	D;D
REVEL	Uncertain	0.43
Sift	Uncertain	0.022	D;D
Sift4G	Benign	0.10	T;T
Polyphen		0.98	D;D
Vest4		0.45
MutPred		0.42		Loss of disorder (P = 0.0206);Loss of disorder (P = 0.0206);
MVP		0.60
MPC		0.15
ClinPred		0.86	D
GERP RS		6.1
Varity_R		0.14
gMVP		0.45

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: chr11-118130808;