17-19384661-C-T

Position:

chr17-19384661-C-T

Variant summary

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

The ENST00000299610.5(MFAP4):c.569G>A(p.Arg190Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00007 in 1,614,054 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00028 ( 1 hom., cov: 32)

Exomes 𝑓: 0.000049 ( 0 hom. )

Consequence

MFAP4
ENST00000299610.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.24

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=0.16166931).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MFAP4	NM_002404.3 linkuse as main transcript	c.569G>A	p.Arg190Gln	missense_variant	6/6	ENST00000299610.5	NP_002395.1	P55083-1
MFAP4	NM_001198695.2 linkuse as main transcript	c.641G>A	p.Arg214Gln	missense_variant	6/6		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.569G>A	p.Arg190Gln	missense_variant	6/6	1	NM_002404.3	ENSP00000299610.5	P55083-1
MFAP4	ENST00000497081.6 linkuse as main transcript	c.644G>A	p.Arg215Gln	missense_variant	5/5	1		ENSP00000468578.1	K7ES70
MFAP4	ENST00000395592.6 linkuse as main transcript	c.641G>A	p.Arg214Gln	missense_variant	6/6	1		ENSP00000378957.2	P55083-2
MFAP4	ENST00000571210.1 linkuse as main transcript	n.680G>A		non_coding_transcript_exon_variant	5/5	5

Frequencies

GnomAD3 genomes

AF:

0.000276

AC:

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00209

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000716

AC:

AN:

251410

Hom.:

AF XY:

0.0000515

AC XY:

AN XY:

135876

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000260

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:

0.0000704

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000486

AC:

AN:

1461866

Hom.:

Cov.:

AF XY:

0.0000440

AC XY:

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000246

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000176

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000387

Gnomad4 OTH exome

AF:

0.000116

GnomAD4 genome

AF:

0.000276

AC:

AN:

152188

Hom.:

Cov.:

AF XY:

0.000336

AC XY:

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00209

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000670

Hom.:

Bravo

AF:

0.000238

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

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 26, 2022

The c.641G>A (p.R214Q) alteration is located in exon 6 (coding exon 6) of the MFAP4 gene. This alteration results from a G to A substitution at nucleotide position 641, causing the arginine (R) at amino acid position 214 to be replaced by a glutamine (Q). 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

0.10

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.42

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.074

T;.;T

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.18

FATHMM_MKL

Benign

0.60

LIST_S2

Uncertain

0.92

D;D;D

M_CAP

Benign

0.075

MetaRNN

Benign

0.16

T;T;T

MetaSVM

Benign

-0.62

MutationAssessor

Benign

0.92

.;.;L

MutationTaster

Benign

0.99

D;D;D

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-1.9

.;N;N

REVEL

Benign

0.20

Sift

Benign

0.41

.;T;T

Sift4G

Benign

0.31

T;T;T

Polyphen

0.13

.;.;B

Vest4

0.056

MutPred

0.62

.;.;Gain of sheet (P = 0.0827);

MVP

0.31

MPC

0.57

ClinPred

0.077

GERP RS

3.0

Varity_R

0.095

gMVP

0.81

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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