Variant 17-19386775-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_002404.3(MFAP4):c.70G>A(p.Gly24Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000381 in 1,574,786 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000030 ( 0 hom. )

Consequence

MFAP4
NM_002404.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.28

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04712832).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MFAP4	NM_002404.3 linkuse as main transcript	c.70G>A	p.Gly24Arg	missense_variant	2/6	ENST00000299610.5	NP_002395.1
MFAP4	NM_001198695.2 linkuse as main transcript	c.142G>A	p.Gly48Arg	missense_variant	2/6		NP_001185624.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MFAP4	ENST00000299610.5 linkuse as main transcript	c.70G>A	p.Gly24Arg	missense_variant	2/6	1	NM_002404.3	ENSP00000299610	P1	P55083-1
MFAP4	ENST00000497081.6 linkuse as main transcript	c.145G>A	p.Gly49Arg	missense_variant	1/5	1		ENSP00000468578
MFAP4	ENST00000395592.6 linkuse as main transcript	c.142G>A	p.Gly48Arg	missense_variant	2/6	1		ENSP00000378957		P55083-2
MFAP4	ENST00000571210.1 linkuse as main transcript	n.105G>A		non_coding_transcript_exon_variant	2/5	5

Frequencies

GnomAD3 genomes

AF:

0.000112

AC:

AN:

152098

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000427

AC:

AN:

187404

Hom.:

AF XY:

0.0000199

AC XY:

AN XY:

100436

show subpopulations

Gnomad AFR exome

AF:

0.000465

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:

0.0000377

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000302

AC:

AN:

1422688

Hom.:

Cov.:

AF XY:

0.0000284

AC XY:

AN XY:

703876

show subpopulations

Gnomad4 AFR exome

AF:

0.000122

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000247

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000320

Gnomad4 OTH exome

AF:

0.0000339

GnomAD4 genome

AF:

0.000112

AC:

AN:

152098

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74300

show subpopulations

Gnomad4 AFR

AF:

0.000338

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000403

Hom.:

Bravo

AF:

0.000140

ESP6500AA

AF:

0.000919

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000335

AC:

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

Jun 16, 2022

The c.142G>A (p.G48R) alteration is located in exon 2 (coding exon 2) of the MFAP4 gene. This alteration results from a G to A substitution at nucleotide position 142, causing the glycine (G) at amino acid position 48 to be replaced by an arginine (R). 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

0.16

BayesDel_addAF

Benign

0.011

BayesDel_noAF

Benign

-0.22

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.17

T;.;T

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.33

FATHMM_MKL

Benign

0.52

LIST_S2

Benign

0.71

T;T;T

M_CAP

Benign

0.022

MetaRNN

Benign

0.047

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

.;.;N

MutationTaster

Benign

0.87

N;N;N

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-0.030

.;N;N

REVEL

Benign

0.077

Sift

Benign

0.050

.;D;T

Sift4G

Benign

0.14

T;T;T

Polyphen

0.0

.;.;B

Vest4

0.27

MutPred

0.45

.;.;Gain of solvent accessibility (P = 0.019);

MVP

0.12

MPC

0.53

ClinPred

0.12

GERP RS

3.9

Varity_R

0.080

gMVP

0.64

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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