Genetic Variant NM_003953.6:c.14C>A (chr1-167722165-C-A) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_003953.6(MPZL1):c.14C>A(p.Ala5Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000487 in 1,236,270 control chromosomes in the GnomAD database, including 1 homozygotes. 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: 𝑓 0.00021 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00053 ( 0 hom. )

Consequence

MPZL1
NM_003953.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0630

Publications

0 publications found

Variant links:

Genes affected

MPZL1 (HGNC:7226): (myelin protein zero like 1) Predicted to enable structural molecule activity. Predicted to be involved in cell-cell signaling and transmembrane receptor protein tyrosine kinase signaling pathway. Predicted to act upstream of or within positive regulation of cell migration. Located in cell surface and focal adhesion. [provided by Alliance of Genome Resources, Apr 2022]

MPZL1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.3276676).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003953.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MPZL1	NM_003953.6	MANE Select	c.14C>A	p.Ala5Asp	missense	Exon 1 of 6	NP_003944.1	A8K5D4
MPZL1	NM_024569.5		c.14C>A	p.Ala5Asp	missense	Exon 1 of 5	NP_078845.3
MPZL1	NM_001146191.2		c.14C>A	p.Ala5Asp	missense	Exon 1 of 3	NP_001139663.1	O95297-5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MPZL1	ENST00000359523.7	TSL:1 MANE Select	c.14C>A	p.Ala5Asp	missense	Exon 1 of 6	ENSP00000352513.2	O95297-1
MPZL1	ENST00000474859.5	TSL:1	c.14C>A	p.Ala5Asp	missense	Exon 1 of 5	ENSP00000420455.1	O95297-3
MPZL1	ENST00000448405.5	TSL:1	n.14C>A		non_coding_transcript_exon	Exon 1 of 5	ENSP00000399490.1	F8WFC4

Frequencies

GnomAD3 genomes

AF:

0.000211

AC:

AN:

151932

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000368

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000526

AC:

570

AN:

1084338

Hom.:

Cov.:

AF XY:

0.000531

AC XY:

272

AN XY:

512580

show subpopulations

African (AFR)

AF:

0.0000872

AC:

AN:

22942

American (AMR)

AF:

0.00

AC:

AN:

8382

Ashkenazi Jewish (ASJ)

AF:

0.0000698

AC:

AN:

14328

East Asian (EAS)

AF:

0.00

AC:

AN:

26522

South Asian (SAS)

AF:

0.00

AC:

AN:

19624

European-Finnish (FIN)

AF:

0.00

AC:

AN:

25036

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3336

European-Non Finnish (NFE)

AF:

0.000604

AC:

556

AN:

920474

Other (OTH)

AF:

0.000252

AC:

AN:

43694

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

114

152

190

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

104

130

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000211

AC:

AN:

151932

Hom.:

Cov.:

AF XY:

0.000189

AC XY:

AN XY:

74218

show subpopulations

African (AFR)

AF:

0.000145

AC:

AN:

41360

American (AMR)

AF:

0.00

AC:

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5158

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.000368

AC:

AN:

67944

Other (OTH)

AF:

0.00

AC:

AN:

2084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.000200

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.0036

BayesDel_noAF

Benign

-0.24

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.023

Eigen

Benign

-0.85

Eigen_PC

Benign

-0.89

FATHMM_MKL

Benign

0.060

LIST_S2

Benign

0.70

M_CAP

Pathogenic

0.84

MetaRNN

Benign

0.33

MetaSVM

Benign

-0.64

MutationAssessor

Benign

0.90

PhyloP100

0.063

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-0.67

REVEL

Benign

0.14

Sift

Uncertain

0.014

Sift4G

Benign

0.10

Polyphen

0.028

Vest4

0.29

MutPred

0.15

Gain of loop (P = 0.1081)

MVP

0.99

MPC

0.63

ClinPred

0.96

GERP RS

2.3

PromoterAI

-0.022

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.12

gMVP

0.32

Mutation Taster

=82/18

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over