chr11-118246303-G-A

Variant names:

• chr11-118246303-G-A
• rs11216831
• NM_198275.3:c.73+5919C>T

Variant summary

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

The NM_198275.3(MPZL3):​c.73+5919C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0449 in 152,214 control chromosomes in the GnomAD database, including 238 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 0.045 (238 hom., cov: 32)
• Consequence: MPZL3 NM_198275.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.458
• Publications: 6 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0666 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MPZL3	NM_198275.3	c.73+5919C>T		intron_variant	Intron 1 of 5	ENST00000278949.9	NP_938016.1
MPZL3	NM_001286152.2	c.73+5919C>T		intron_variant	Intron 1 of 5		NP_001273081.1
MPZL3	NR_104404.2	n.144+5919C>T		intron_variant	Intron 1 of 2
MPZL3	NR_104405.2	n.144+5919C>T		intron_variant	Intron 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MPZL3	ENST00000278949.9	c.73+5919C>T		intron_variant	Intron 1 of 5	1	NM_198275.3	ENSP00000278949.4
MPZL3	ENST00000527472.1	c.73+5919C>T		intron_variant	Intron 1 of 5	1		ENSP00000432106.1
MPZL3	ENST00000525386.5	c.73+5919C>T		intron_variant	Intron 1 of 2	1		ENSP00000434636.1
MPZL3	ENST00000446386.2	n.73+5919C>T		intron_variant	Intron 1 of 4	2		ENSP00000393594.2

Frequencies

GnomAD3 genomes AF: 0.0449 AC: 6830 AN: 152096 Hom.: 238 Cov.: 32

Gnomad AFR AF: 0.0135

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.0301

Gnomad ASJ AF: 0.0340

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0371

Gnomad FIN AF: 0.0710

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0683

Gnomad OTH AF: 0.0460

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

GnomAD4 genome AF: 0.0449 AC: 6828 AN: 152214 Hom.: 238 Cov.: 32 AF XY: 0.0438 AC XY: 3263 AN XY: 74414

African (AFR) AF: 0.0135 AC: 560 AN: 41544

American (AMR) AF: 0.0301 AC: 460 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0340 AC: 118 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5182

South Asian (SAS) AF: 0.0369 AC: 178 AN: 4826

European-Finnish (FIN) AF: 0.0710 AC: 751 AN: 10576

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0683 AC: 4642 AN: 68010

Other (OTH) AF: 0.0455 AC: 96 AN: 2108

Alfa AF: 0.0498 Hom.: 196

Bravo AF: 0.0418

Asia WGS AF: 0.0120 AC: 42 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.3
DANN	Benign	0.84
PhyloP100		-0.46
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: rs11216831; hg19: chr11-118117018;