NM_003953.6:c.92-19423A>C

Variant names:

• chr1-167746160-A-C
• rs2213883
• NM_003953.6:c.92-19423A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003953.6(MPZL1):​c.92-19423A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 152,060 control chromosomes in the GnomAD database, including 2,343 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.16 (2343 hom., cov: 32)
• Consequence: MPZL1 NM_003953.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.142
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.207 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPZL1	NM_003953.6	MANE Select	c.92-19423A>C		intron	N/A	NP_003944.1
	MPZL1	NM_024569.5		c.92-19423A>C		intron	N/A	NP_078845.3
	MPZL1	NM_001146191.2		c.92-19423A>C		intron	N/A	NP_001139663.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPZL1	ENST00000359523.7	TSL:1 MANE Select	c.92-19423A>C		intron	N/A	ENSP00000352513.2
	MPZL1	ENST00000474859.5	TSL:1	c.92-19423A>C		intron	N/A	ENSP00000420455.1
	MPZL1	ENST00000448405.5	TSL:1	n.92-19423A>C		intron	N/A	ENSP00000399490.1

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24615 AN: 151942 Hom.: 2339 Cov.: 32

Gnomad AFR AF: 0.0750

Gnomad AMI AF: 0.295

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.269

Gnomad EAS AF: 0.159

Gnomad SAS AF: 0.186

Gnomad FIN AF: 0.175

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.180

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.162 AC: 24616 AN: 152060 Hom.: 2343 Cov.: 32 AF XY: 0.164 AC XY: 12180 AN XY: 74312

African (AFR) AF: 0.0750 AC: 3113 AN: 41524

American (AMR) AF: 0.213 AC: 3253 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.269 AC: 933 AN: 3470

East Asian (EAS) AF: 0.159 AC: 822 AN: 5180

South Asian (SAS) AF: 0.186 AC: 898 AN: 4818

European-Finnish (FIN) AF: 0.175 AC: 1843 AN: 10522

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.192 AC: 13042 AN: 67970

Other (OTH) AF: 0.179 AC: 378 AN: 2110

Alfa AF: 0.179 Hom.: 5516

Bravo AF: 0.165

Asia WGS AF: 0.158 AC: 551 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	7.4
DANN	Benign	0.89
PhyloP100		0.14
Mutation Taster		=100/0	polymorphism (auto)

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: rs2213883; hg19: chr1-167715397;