1-167776122-G-A

Variant names:

• chr1-167776122-G-A
• rs1024099233
• NM_003953.6:c.664G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003953.6(MPZL1):​c.664G>A​(p.Asp222Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000298 in 1,612,502 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000027 (0 hom.)
• Consequence: MPZL1 NM_003953.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.37
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2546863).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPZL1	NM_003953.6	MANE Select	c.664G>A	p.Asp222Asn	missense	Exon 5 of 6	NP_003944.1	A8K5D4
	MPZL1	NM_024569.5		c.605+2754G>A		intron	N/A	NP_078845.3
	MPZL1	NM_001146191.2		c.258+10373G>A		intron	N/A	NP_001139663.1	O95297-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPZL1	ENST00000359523.7	TSL:1 MANE Select	c.664G>A	p.Asp222Asn	missense	Exon 5 of 6	ENSP00000352513.2	O95297-1
	MPZL1	ENST00000474859.5	TSL:1	c.605+2754G>A		intron	N/A	ENSP00000420455.1	O95297-3
	MPZL1	ENST00000367853.3	TSL:1	c.527+2754G>A		intron	N/A	ENSP00000356827.3	Q9UEL6

Frequencies

GnomAD3 genomes AF: 0.0000526 AC: 8 AN: 152116 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000279 AC: 7 AN: 250458 AF XY: 0.0000295

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000618

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000274 AC: 40 AN: 1460386 Hom.: 0 Cov.: 30 AF XY: 0.0000303 AC XY: 22 AN XY: 726508

African (AFR) AF: 0.000120 AC: 4 AN: 33406

American (AMR) AF: 0.0000224 AC: 1 AN: 44614

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26100

East Asian (EAS) AF: 0.00 AC: 0 AN: 39534

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86090

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53372

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.0000270 AC: 30 AN: 1111200

Other (OTH) AF: 0.0000332 AC: 2 AN: 60306

GnomAD4 genome AF: 0.0000526 AC: 8 AN: 152116 Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4 AN XY: 74326

African (AFR) AF: 0.0000242 AC: 1 AN: 41402

American (AMR) AF: 0.00 AC: 0 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.000196 Hom.: 0

Bravo AF: 0.0000264

EpiCase AF: 0.0000547

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.041	T
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.041	D
MetaRNN	Benign	0.25	T
MetaSVM	Uncertain	0.55	D
MutationAssessor	Benign	0.97	L
PhyloP100		2.4
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-1.0	N
REVEL	Uncertain	0.30
Sift	Benign	0.22	T
Sift4G	Benign	0.065	T
Polyphen		1.0	D
Vest4		0.20
MutPred		0.14		Loss of ubiquitination at K218 (P = 0.0184)
MVP		1.0
MPC		0.46
ClinPred		0.37	T
GERP RS		4.4
Varity_R		0.10
gMVP		0.50
Mutation Taster		=89/11	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs1024099233; hg19: chr1-167745359;