1-167722239-C-T

Variant names:

• chr1-167722239-C-T
• rs1660044779
• NM_003953.6:c.88C>T

Variant summary

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

The NM_003953.6(MPZL1):​c.88C>T​(p.Leu30Phe) 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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MPZL1 NM_003953.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.759

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]

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=0.32460526).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MPZL1	NM_003953.6	c.88C>T	p.Leu30Phe	missense_variant	Exon 1 of 6	ENST00000359523.7	NP_003944.1
MPZL1	NM_024569.5	c.88C>T	p.Leu30Phe	missense_variant	Exon 1 of 5		NP_078845.3
MPZL1	NM_001146191.2	c.88C>T	p.Leu30Phe	missense_variant	Exon 1 of 3		NP_001139663.1
MPZL1	XM_047433610.1	c.-367C>T		5_prime_UTR_variant	Exon 1 of 7		XP_047289566.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MPZL1	ENST00000359523.7	c.88C>T	p.Leu30Phe	missense_variant	Exon 1 of 6	1	NM_003953.6	ENSP00000352513.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1086906 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 513630

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 20, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.88C>T (p.L30F) alteration is located in exon 1 (coding exon 1) of the MPZL1 gene. This alteration results from a C to T substitution at nucleotide position 88, causing the leucine (L) at amino acid position 30 to be replaced by a phenylalanine (F). 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	Benign	0.063
BayesDel_addAF	Benign	-0.022	T
BayesDel_noAF	Benign	-0.27
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.038	T;.;.
Eigen	Benign	0.0081
Eigen_PC	Benign	-0.0058
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.79	T;T;T
M_CAP	Pathogenic	0.30	D
MetaRNN	Benign	0.32	T;T;T
MetaSVM	Benign	-0.75	T
MutationAssessor	Benign	0.90	L;L;L
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-0.91	N;N;N
REVEL	Benign	0.27
Sift	Benign	0.031	D;D;T
Sift4G	Uncertain	0.043	D;T;T
Polyphen		0.84	P;.;D
Vest4		0.37
MutPred		0.47		Gain of catalytic residue at L30 (P = 0.0242);Gain of catalytic residue at L30 (P = 0.0242);Gain of catalytic residue at L30 (P = 0.0242);
MVP		0.97
MPC		1.3
ClinPred		0.61	D
GERP RS		3.2
Varity_R		0.26
gMVP		0.26

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs1660044779; hg19: chr1-167691476;