rs144095475

Variant names:

• chr11-118240326-C-A
• rs144095475
• NM_198275.3:c.125G>T

Your query was ambiguous. Multiple possible variants found:

• chr11-118240326-C-A
• chr11-118240326-C-T

Variant summary

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

The NM_198275.3(MPZL3):​c.125G>T​(p.Gly42Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,456,212 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. G42D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: MPZL3 NM_198275.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.36
• Publications: 1 publications found

Genes affected

MPZL3 (HGNC:27279): (myelin protein zero like 3) Predicted to be involved in cell adhesion. Predicted to act upstream of or within extracellular matrix organization and hair cycle. Predicted to be integral component of membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198275.3. 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
	MPZL3	NM_198275.3	MANE Select	c.125G>T	p.Gly42Val	missense	Exon 2 of 6	NP_938016.1	Q6UWV2-1
	MPZL3	NM_001286152.2		c.89G>T	p.Gly30Val	missense	Exon 2 of 6	NP_001273081.1	Q6UWV2-2
	MPZL3	NR_104405.2		n.196G>T		non_coding_transcript_exon	Exon 2 of 5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPZL3	ENST00000278949.9	TSL:1 MANE Select	c.125G>T	p.Gly42Val	missense	Exon 2 of 6	ENSP00000278949.4	Q6UWV2-1
	MPZL3	ENST00000527472.1	TSL:1	c.89G>T	p.Gly30Val	missense	Exon 2 of 6	ENSP00000432106.1	Q6UWV2-2
	MPZL3	ENST00000525386.5	TSL:1	c.74-6803G>T		intron	N/A	ENSP00000434636.1	E9PPB1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1456212 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 724368

African (AFR) AF: 0.00 AC: 0 AN: 33210

American (AMR) AF: 0.00 AC: 0 AN: 43224

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26054

East Asian (EAS) AF: 0.00 AC: 0 AN: 39332

South Asian (SAS) AF: 0.00 AC: 0 AN: 84926

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53376

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 9.01e-7 AC: 1 AN: 1110180

Other (OTH) AF: 0.00 AC: 0 AN: 60154

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000165 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.65
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.042	D
MetaRNN	Uncertain	0.51	D
MetaSVM	Benign	-0.79	T
MutationAssessor	Benign	0.28	N
PhyloP100		1.4
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.28
Sift	Uncertain	0.0070	D
Sift4G	Benign	0.21	T
Polyphen		1.0	D
Vest4		0.63
MVP		0.36
MPC		0.42
ClinPred		0.94	D
GERP RS		5.5
Varity_R		0.44
gMVP		0.85
Mutation Taster		=69/31	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: rs144095475; hg19: chr11-118111041;