rs3767444

Variant names:

• chr1-167723379-C-T
• rs3767444
• NM_003953.6:c.91+1137C>T

Variant summary

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

The NM_003953.6(MPZL1):​c.91+1137C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 152,112 control chromosomes in the GnomAD database, including 6,379 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 0.29 (6379 hom., cov: 33)
• Consequence: MPZL1 NM_003953.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00400
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.3 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.91+1137C>T		intron	N/A	NP_003944.1
	MPZL1	NM_024569.5		c.91+1137C>T		intron	N/A	NP_078845.3
	MPZL1	NM_001146191.2		c.91+1137C>T		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.91+1137C>T		intron	N/A	ENSP00000352513.2
	MPZL1	ENST00000474859.5	TSL:1	c.91+1137C>T		intron	N/A	ENSP00000420455.1
	MPZL1	ENST00000448405.5	TSL:1	n.91+1137C>T		intron	N/A	ENSP00000399490.1

Frequencies

GnomAD3 genomes AF: 0.288 AC: 43811 AN: 151994 Hom.: 6368 Cov.: 33

Gnomad AFR AF: 0.304

Gnomad AMI AF: 0.171

Gnomad AMR AF: 0.268

Gnomad ASJ AF: 0.273

Gnomad EAS AF: 0.266

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.247

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.292

Gnomad OTH AF: 0.309

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

GnomAD4 genome AF: 0.288 AC: 43873 AN: 152112 Hom.: 6379 Cov.: 33 AF XY: 0.285 AC XY: 21219 AN XY: 74360

African (AFR) AF: 0.304 AC: 12615 AN: 41468

American (AMR) AF: 0.268 AC: 4096 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.273 AC: 948 AN: 3472

East Asian (EAS) AF: 0.266 AC: 1379 AN: 5178

South Asian (SAS) AF: 0.299 AC: 1441 AN: 4822

European-Finnish (FIN) AF: 0.247 AC: 2609 AN: 10564

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.292 AC: 19877 AN: 68002

Other (OTH) AF: 0.310 AC: 655 AN: 2114

Alfa AF: 0.288 Hom.: 3835

Bravo AF: 0.287

Asia WGS AF: 0.289 AC: 1004 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.4
DANN	Benign	0.27
PhyloP100		0.0040
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: rs3767444; hg19: chr1-167692616;