Variant chr17-19387057-C-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000299610.5(MFAP4):c.6+93G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000411 in 1,521,438 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00035 ( 0 hom., cov: 28)

Exomes 𝑓: 0.00042 ( 0 hom. )

Consequence

MFAP4
ENST00000299610.5 intron

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.316

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:

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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=0.00643155).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MFAP4	NM_002404.3 linkuse as main transcript	c.6+93G>T		intron_variant		ENST00000299610.5	NP_002395.1	P55083-1
MFAP4	NM_001198695.2 linkuse as main transcript	c.62G>T	p.Gly21Val	missense_variant	1/6		NP_001185624.1	P55083-2A0A024QZ34

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MFAP4	ENST00000395592.6 linkuse as main transcript	c.62G>T	p.Gly21Val	missense_variant	1/6	1		ENSP00000378957.2	P55083-2
MFAP4	ENST00000299610.5 linkuse as main transcript	c.6+93G>T		intron_variant		1	NM_002404.3	ENSP00000299610.5	P55083-1
MFAP4	ENST00000571210.1 linkuse as main transcript	n.41+93G>T		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.000350

AC:

AN:

142724

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000771

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000291

Gnomad ASJ

AF:

0.00442

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000394

Gnomad OTH

AF:

0.00102

GnomAD3 exomes

AF:

0.000443

AC:

110

AN:

248096

Hom.:

AF XY:

0.000469

AC XY:

AN XY:

134366

show subpopulations

Gnomad AFR exome

AF:

0.0000629

Gnomad AMR exome

AF:

0.000117

Gnomad ASJ exome

AF:

0.00570

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000384

Gnomad OTH exome

AF:

0.000827

GnomAD4 exome

AF:

0.000417

AC:

575

AN:

1378572

Hom.:

Cov.:

AF XY:

0.000413

AC XY:

283

AN XY:

684554

show subpopulations

Gnomad4 AFR exome

AF:

0.000161

Gnomad4 AMR exome

AF:

0.0000955

Gnomad4 ASJ exome

AF:

0.00595

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000369

Gnomad4 OTH exome

AF:

0.000675

GnomAD4 genome

AF:

0.000350

AC:

AN:

142866

Hom.:

Cov.:

AF XY:

0.000319

AC XY:

AN XY:

69014

show subpopulations

Gnomad4 AFR

AF:

0.0000768

Gnomad4 AMR

AF:

0.000290

Gnomad4 ASJ

AF:

0.00442

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000394

Gnomad4 OTH

AF:

0.00101

Alfa

AF:

0.000752

Hom.:

Bravo

AF:

0.000393

ExAC

AF:

0.000305

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000833

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

Dec 21, 2022

The c.62G>T (p.G21V) alteration is located in exon 1 (coding exon 1) of the MFAP4 gene. This alteration results from a G to T substitution at nucleotide position 62, causing the glycine (G) at amino acid position 21 to be replaced by a valine (V). 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

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Uncertain

0.99

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.47

M_CAP

Benign

0.010

MetaRNN

Benign

0.0064

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.24

REVEL

Benign

0.14

Sift

Uncertain

0.014

Sift4G

Benign

0.24

Vest4

0.46

MVP

0.16

MPC

1.4

ClinPred

0.032

GERP RS

-6.1

gMVP

0.47

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