Variant 11-119342980-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000619721.6(MFRP):c.1148C>A(p.Pro383His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,455,708 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/17 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. P383L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

MFRP
ENST00000619721.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.66

Variant links:

Genes affected

MFRP (HGNC:18121): (membrane frizzled-related protein) This gene encodes a member of the frizzled-related protein family. The encoded protein plays an important role in eye development and mutations in this gene have been associated with nanophthalmos, posterior microphthalmia, retinitis pigmentosa, foveoschisis, and optic disc drusen. The protein is encoded by a bicistronic transcript which also encodes C1q and tumor necrosis factor related protein 5 (C1QTNF5). [provided by RefSeq, Jun 2013]

MFRP links:

C1QTNF5 (HGNC:):

C1QTNF5 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.21227401).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MFRP	NM_031433.4 linkuse as main transcript	c.1148C>A	p.Pro383His	missense_variant	10/15	ENST00000619721.6	NP_113621.1
C1QTNF5	NM_015645.5 linkuse as main transcript	c.-1489C>A		5_prime_UTR_variant	10/15		NP_056460.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MFRP	ENST00000619721.6 linkuse as main transcript	c.1148C>A	p.Pro383His	missense_variant	10/15	1	NM_031433.4	ENSP00000481824	P1	Q9BY79-1
MFRP	ENST00000360167.4 linkuse as main transcript	c.922C>A	p.Pro308Thr	missense_variant	8/10	2		ENSP00000353291		Q9BY79-2
MFRP	ENST00000449574.7 linkuse as main transcript	c.2C>A	p.Ter1=	coding_sequence_variant	1/4	5		ENSP00000391664

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000847

AC:

AN:

236052

Hom.:

AF XY:

0.00

AC XY:

AN XY:

128500

show subpopulations

Gnomad AFR exome

AF:

0.0000663

Gnomad AMR exome

AF:

0.0000299

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1455708

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

723738

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000683

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.22

Eigen

Benign

-0.66

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.61

LIST_S2

Benign

0.45

M_CAP

Benign

0.016

MetaRNN

Benign

0.21

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.3

MutationTaster

Benign

1.0

N;N;N;N

Sift4G

Uncertain

0.0080

Polyphen

1.0

Vest4

0.24

MutPred

0.47

Loss of glycosylation at P383 (P = 0.0589);

MVP

0.29

ClinPred

0.55

GERP RS

0.56

Varity_R

0.050

gMVP

0.42

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over