11-118240258-T-C

Variant names:

• chr11-118240258-T-C
• rs781256738
• NM_198275.3:c.193A>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_198275.3(MPZL3):​c.193A>G​(p.Thr65Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MPZL3 NM_198275.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.58
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35525757).

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.193A>G	p.Thr65Ala	missense	Exon 2 of 6	NP_938016.1	Q6UWV2-1
	MPZL3	NM_001286152.2		c.157A>G	p.Thr53Ala	missense	Exon 2 of 6	NP_001273081.1	Q6UWV2-2
	MPZL3	NR_104405.2		n.264A>G		non_coding_transcript_exon	Exon 2 of 5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPZL3	ENST00000278949.9	TSL:1 MANE Select	c.193A>G	p.Thr65Ala	missense	Exon 2 of 6	ENSP00000278949.4	Q6UWV2-1
	MPZL3	ENST00000527472.1	TSL:1	c.157A>G	p.Thr53Ala	missense	Exon 2 of 6	ENSP00000432106.1	Q6UWV2-2
	MPZL3	ENST00000525386.5	TSL:1	c.74-6735A>G		intron	N/A	ENSP00000434636.1	E9PPB1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000415 AC: 1 AN: 240896 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: 0.00000899

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

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	Benign	0.29
BayesDel_addAF	Uncertain	0.059	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.11
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.36	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.2	L
PhyloP100		2.6
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.28
Sift	Benign	0.30	T
Sift4G	Benign	0.28	T
Polyphen		0.014	B
Vest4		0.50
MutPred		0.49		Loss of phosphorylation at T65 (P = 0.0626)
MVP		0.35
MPC		0.073
ClinPred		0.25	T
GERP RS		5.6
Varity_R		0.077
gMVP		0.54
Mutation Taster		=86/14	polymorphism

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

Other links and lift over

dbSNP: rs781256738; hg19: chr11-118110973;