1-167765685-C-G

Variant names:

• chr1-167765685-C-G
• rs774611276
• NM_003953.6:c.194C>G

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.194C>G​(p.Thr65Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,024 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T65M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: MPZL1 NM_003953.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.783
• 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=0.2047478).

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.194C>G	p.Thr65Arg	missense	Exon 2 of 6	NP_003944.1	A8K5D4
	MPZL1	NM_024569.5		c.194C>G	p.Thr65Arg	missense	Exon 2 of 5	NP_078845.3
	MPZL1	NM_001146191.2		c.194C>G	p.Thr65Arg	missense	Exon 2 of 3	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.194C>G	p.Thr65Arg	missense	Exon 2 of 6	ENSP00000352513.2	O95297-1
	MPZL1	ENST00000474859.5	TSL:1	c.194C>G	p.Thr65Arg	missense	Exon 2 of 5	ENSP00000420455.1	O95297-3
	MPZL1	ENST00000367853.3	TSL:1	c.116C>G	p.Thr39Arg	missense	Exon 1 of 4	ENSP00000356827.3	Q9UEL6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461024 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726832

African (AFR) AF: 0.00 AC: 0 AN: 33438

American (AMR) AF: 0.00 AC: 0 AN: 44626

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39656

South Asian (SAS) AF: 0.00 AC: 0 AN: 86088

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111534

Other (OTH) AF: 0.00 AC: 0 AN: 60370

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.054	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	5.8
DANN	Benign	0.86
DEOGEN2	Benign	0.057	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.038	N
LIST_S2	Benign	0.76	T
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.44	T
MutationAssessor	Benign	1.1	L
PhyloP100		-0.78
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.25
Sift	Benign	0.059	T
Sift4G	Benign	0.47	T
Polyphen		0.66	P
Vest4		0.19
MutPred		0.57		Gain of MoRF binding (P = 0.0162)
MVP		0.89
MPC		0.94
ClinPred		0.24	T
GERP RS		-3.6
PromoterAI		-0.060	Neutral
Varity_R		0.31
gMVP		0.41
Mutation Taster		=88/12	polymorphism

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: rs774611276; hg19: chr1-167734922;