Genetic Variant ENST00000395592.6:c.62G>C (chr17-19387057-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000395592.6(MFAP4):c.62G>C(p.Gly21Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000029 in 1,378,572 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G21V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 28)

Exomes 𝑓: 0.0000029 ( 0 hom. )

Consequence

MFAP4
ENST00000395592.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.316

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11862281).

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>C		intron	N/A	NP_002395.1	P55083-1
	MFAP4	NM_001198695.2		c.62G>C	p.Gly21Ala	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>C	p.Gly21Ala	missense	Exon 1 of 6	ENSP00000378957.2	P55083-2
MFAP4	ENST00000299610.5	TSL:1 MANE Select	c.6+93G>C		intron	N/A	ENSP00000299610.5	P55083-1
MFAP4	ENST00000885623.1		c.6+93G>C		intron	N/A	ENSP00000555682.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000290

AC:

AN:

1378572

Hom.:

Cov.:

AF XY:

0.00000438

AC XY:

AN XY:

684554

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31134

American (AMR)

AF:

0.00

AC:

AN:

41868

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

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:

0.00

AC:

AN:

5158

European-Non Finnish (NFE)

AF:

0.00000378

AC:

AN:

1057136

Other (OTH)

AF:

0.00

AC:

AN:

54852

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.69

CADD

Benign

(source)

DANN

Uncertain

0.99

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.49

M_CAP

Benign

0.010

MetaRNN

Benign

0.12

MetaSVM

Benign

-1.0

PhyloP100

0.32

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.18

REVEL

Benign

0.073

Sift

Benign

0.22

Sift4G

Benign

1.0

Vest4

0.29

MutPred

0.42

Loss of catalytic residue at G21 (P = 0.077)

MVP

0.32

MPC

1.2

ClinPred

0.80

GERP RS

-6.1

PromoterAI

-0.031

Neutral

(source)

gMVP

0.51

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over