Genetic Variant ENST00000395592.6:c.62G>T (chr17-19387057-C-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000395592.6(MFAP4):c.62G>T(p.Gly21Val) variant causes a missense 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. 15/20 in silico tools predict 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
ENST00000395592.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.316

Publications

1 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00643155).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000395592.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MFAP4	NM_002404.3	MANE Select	c.6+93G>T		intron	N/A	NP_002395.1	P55083-1
	MFAP4	NM_001198695.2		c.62G>T	p.Gly21Val	missense	Exon 1 of 6	NP_001185624.1	P55083-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MFAP4	ENST00000395592.6	TSL:1	c.62G>T	p.Gly21Val	missense	Exon 1 of 6	ENSP00000378957.2	P55083-2
MFAP4	ENST00000299610.5	TSL:1 MANE Select	c.6+93G>T		intron	N/A	ENSP00000299610.5	P55083-1
MFAP4	ENST00000885623.1		c.6+93G>T		intron	N/A	ENSP00000555682.1

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

GnomAD2 exomes

AF:

0.000443

AC:

110

AN:

248096

AF XY:

0.000469

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 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

African (AFR)

AF:

0.000161

AC:

AN:

31134

American (AMR)

AF:

0.0000955

AC:

AN:

41868

Ashkenazi Jewish (ASJ)

AF:

0.00595

AC:

138

AN:

23200

East Asian (EAS)

AF:

0.00

AC:

AN:

33784

South Asian (SAS)

AF:

0.00

AC:

AN:

85082

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46358

Middle Eastern (MID)

AF:

0.000194

AC:

AN:

5158

European-Non Finnish (NFE)

AF:

0.000369

AC:

390

AN:

1057136

Other (OTH)

AF:

0.000675

AC:

AN:

54852

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

119

149

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000350

AC:

AN:

142866

Hom.:

Cov.:

AF XY:

0.000319

AC XY:

AN XY:

69014

show subpopulations

African (AFR)

AF:

0.0000768

AC:

AN:

39046

American (AMR)

AF:

0.000290

AC:

AN:

13780

Ashkenazi Jewish (ASJ)

AF:

0.00442

AC:

AN:

3396

East Asian (EAS)

AF:

0.00

AC:

AN:

4378

South Asian (SAS)

AF:

0.00

AC:

AN:

4206

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8874

Middle Eastern (MID)

AF:

0.00

AC:

AN:

280

European-Non Finnish (NFE)

AF:

0.000394

AC:

AN:

66030

Other (OTH)

AF:

0.00101

AC:

AN:

1988

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000752

Hom.:

Bravo

AF:

0.000393

ExAC

AF:

0.000305

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000833

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.63

CADD

Benign

(source)

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

PhyloP100

0.32

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

PromoterAI

-0.081

Neutral

(source)

gMVP

0.47

Mutation Taster

=98/2

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over