1-167765686-G-A

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_003953.6(MPZL1):c.195G>A(p.Thr65=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00144 in 1,613,348 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0015 (3 hom.)
• Consequence: MPZL1 NM_003953.6 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.70

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 Benign. Variant got -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant 1-167765686-G-A is Benign according to our data. Variant chr1-167765686-G-A is described in ClinVar as [Benign]. Clinvar id is 710258.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.7 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MPZL1	NM_003953.6	c.195G>A	p.Thr65=	synonymous_variant	2/6	ENST00000359523.7
MPZL1	NM_024569.5	c.195G>A	p.Thr65=	synonymous_variant	2/5
MPZL1	NM_001146191.2	c.195G>A	p.Thr65=	synonymous_variant	2/3
MPZL1	XM_047433610.1	c.-178G>A		5_prime_UTR_variant	3/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MPZL1	ENST00000359523.7	c.195G>A	p.Thr65=	synonymous_variant	2/6	1	NM_003953.6	P3

Frequencies

GnomAD3 genomes AF: 0.00127 AC: 193 AN: 152190 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000410

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00105

Gnomad ASJ AF: 0.00432

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00201

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.00151 AC: 378 AN: 250130 Hom.: 1 AF XY: 0.00160 AC XY: 217 AN XY: 135232

Gnomad AFR exome AF: 0.000370

Gnomad AMR exome AF: 0.000998

Gnomad ASJ exome AF: 0.00586

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000428

Gnomad FIN exome AF: 0.000139

Gnomad NFE exome AF: 0.00221

Gnomad OTH exome AF: 0.00197

GnomAD4 exome AF: 0.00146 AC: 2127 AN: 1461040 Hom.: 3 Cov.: 31 AF XY: 0.00147 AC XY: 1069 AN XY: 726812

Gnomad4 AFR exome AF: 0.000508

Gnomad4 AMR exome AF: 0.000964

Gnomad4 ASJ exome AF: 0.00532

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000569

Gnomad4 FIN exome AF: 0.000393

Gnomad4 NFE exome AF: 0.00155

Gnomad4 OTH exome AF: 0.00167

GnomAD4 genome AF: 0.00127 AC: 193 AN: 152308 Hom.: 0 Cov.: 32 AF XY: 0.00122 AC XY: 91 AN XY: 74476

Gnomad4 AFR AF: 0.000409

Gnomad4 AMR AF: 0.00105

Gnomad4 ASJ AF: 0.00432

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00201

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.00168 Hom.: 0

Bravo AF: 0.00125

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

May 09, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	0.25
Dann	Benign	0.60

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

Publications

LitVar

Other links and lift over

dbSNP: rs150711804; hg19: chr1-167734923;