Variant chr17-19386819-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_002404.3(MFAP4):c.26T>C(p.Leu9Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000472 in 1,567,968 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000050 ( 0 hom. )

Consequence

MFAP4
NM_002404.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.642

Variant links:

Genes affected

MFAP4 (HGNC:7035): (microfibril associated protein 4) This gene encodes a protein with similarity to a bovine microfibril-associated protein. The protein has binding specificities for both collagen and carbohydrate. It is thought to be an extracellular matrix protein which is involved in cell adhesion or intercellular interactions. The gene is located within the Smith-Magenis syndrome region. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2010]

MFAP4 links:

MFAP4 (HGNC:):

MFAP4 links:

Genome browser will be placed here

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=0.21526262).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MFAP4	NM_002404.3 linkuse as main transcript	c.26T>C	p.Leu9Pro	missense_variant	2/6	ENST00000299610.5	NP_002395.1	P55083-1
MFAP4	NM_001198695.2 linkuse as main transcript	c.98T>C	p.Leu33Pro	missense_variant	2/6		NP_001185624.1	P55083-2A0A024QZ34

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MFAP4	ENST00000299610.5 linkuse as main transcript	c.26T>C	p.Leu9Pro	missense_variant	2/6	1	NM_002404.3	ENSP00000299610.5	P55083-1
MFAP4	ENST00000497081.6 linkuse as main transcript	c.101T>C	p.Leu34Pro	missense_variant	1/5	1		ENSP00000468578.1	K7ES70
MFAP4	ENST00000395592.6 linkuse as main transcript	c.98T>C	p.Leu33Pro	missense_variant	2/6	1		ENSP00000378957.2	P55083-2
MFAP4	ENST00000571210.1 linkuse as main transcript	n.61T>C		non_coding_transcript_exon_variant	2/5	5

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000171

AC:

AN:

175018

Hom.:

AF XY:

0.0000214

AC XY:

AN XY:

93634

show subpopulations

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000416

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000501

AC:

AN:

1415806

Hom.:

Cov.:

AF XY:

0.0000429

AC XY:

AN XY:

699914

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000200

Gnomad4 NFE exome

AF:

0.0000606

Gnomad4 OTH exome

AF:

0.0000682

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152162

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.0000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 23, 2023

The c.98T>C (p.L33P) alteration is located in exon 2 (coding exon 2) of the MFAP4 gene. This alteration results from a T to C substitution at nucleotide position 98, causing the leucine (L) at amino acid position 33 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.094

BayesDel_noAF

Benign

-0.25

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.10

T;.;T

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.27

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.56

T;T;T

M_CAP

Benign

0.021

MetaRNN

Benign

0.22

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.69

.;.;N

PrimateAI

Benign

0.47

PROVEAN

Benign

-1.4

.;N;N

REVEL

Benign

0.19

Sift

Benign

0.24

.;T;T

Sift4G

Benign

0.13

T;D;D

Polyphen

0.0

.;.;B

Vest4

0.42

MutPred

0.66

.;.;Gain of loop (P = 0.002);

MVP

0.57

MPC

1.4

ClinPred

0.45

GERP RS

3.9

Varity_R

0.65

gMVP

0.60

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over