11-118237173-C-A

Variant names:

• chr11-118237173-C-A
• rs1200368574
• NM_198275.3:c.328G>T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_198275.3(MPZL3):​c.328G>T​(p.Asp110Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.0000186 in 1,613,952 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000020 (0 hom.)
• Consequence: MPZL3 NM_198275.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.10
• Publications: 0 publications found

Genes affected

MPZL3 (HGNC:27279): (myelin protein zero like 3) Predicted to be involved in cell adhesion. Predicted to act upstream of or within extracellular matrix organization and hair cycle. Predicted to be integral component of membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.92

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198275.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPZL3	NM_198275.3	MANE Select	c.328G>T	p.Asp110Tyr	missense	Exon 3 of 6	NP_938016.1	Q6UWV2-1
	MPZL3	NM_001286152.2		c.292G>T	p.Asp98Tyr	missense	Exon 3 of 6	NP_001273081.1	Q6UWV2-2
	MPZL3	NR_104404.2		n.145-3650G>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPZL3	ENST00000278949.9	TSL:1 MANE Select	c.328G>T	p.Asp110Tyr	missense	Exon 3 of 6	ENSP00000278949.4	Q6UWV2-1
	MPZL3	ENST00000527472.1	TSL:1	c.292G>T	p.Asp98Tyr	missense	Exon 3 of 6	ENSP00000432106.1	Q6UWV2-2
	MPZL3	ENST00000525386.5	TSL:1	c.74-3650G>T		intron	N/A	ENSP00000434636.1	E9PPB1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152160 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000796 AC: 2 AN: 251344 AF XY: 0.00

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000198 AC: 29 AN: 1461792 Hom.: 0 Cov.: 37 AF XY: 0.0000193 AC XY: 14 AN XY: 727212

African (AFR) AF: 0.00 AC: 0 AN: 33470

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000261 AC: 29 AN: 1111934

Other (OTH) AF: 0.00 AC: 0 AN: 60390

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152160 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74326

African (AFR) AF: 0.00 AC: 0 AN: 41434

American (AMR) AF: 0.00 AC: 0 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000434 Hom.: 0

Bravo AF: 0.00000378

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.86
BayesDel_addAF	Pathogenic	0.35	D
BayesDel_noAF	Pathogenic	0.28
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.70	D
Eigen	Pathogenic	0.86
Eigen_PC	Pathogenic	0.84
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.89	D
M_CAP	Uncertain	0.13	D
MetaRNN	Pathogenic	0.92	D
MetaSVM	Uncertain	0.11	D
MutationAssessor	Pathogenic	3.5	H
PhyloP100		5.1
PrimateAI	Uncertain	0.56	T
PROVEAN	Pathogenic	-8.5	D
REVEL	Uncertain	0.63
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.96
MutPred		0.74		Loss of ubiquitination at K108 (P = 0.0435)
MVP		0.55
MPC		0.42
ClinPred		1.0	D
GERP RS		6.0
Varity_R		0.93
gMVP		0.82
Mutation Taster		=28/72	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1200368574; hg19: chr11-118107888;