dbSNP rs368593393: MFAP4:p.Gly24Arg (chr17-19386775-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_002404.3(MFAP4):c.70G>C(p.Gly24Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000703 in 1,422,688 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

MFAP4
NM_002404.3 missense

Scores

Clinical Significance

Not reported in ClinVar

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:

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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=0.13192993).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MFAP4	NM_002404.3 link	c.70G>C	p.Gly24Arg	missense_variant	Exon 2 of 6	ENST00000299610.5	NP_002395.1	P55083-1
MFAP4	NM_001198695.2 link	c.142G>C	p.Gly48Arg	missense_variant	Exon 2 of 6		NP_001185624.1	P55083-2A0A024QZ34

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MFAP4	ENST00000299610.5 link	c.70G>C	p.Gly24Arg	missense_variant	Exon 2 of 6	1	NM_002404.3	ENSP00000299610.5	P55083-1
MFAP4	ENST00000497081.6 link	c.145G>C	p.Gly49Arg	missense_variant	Exon 1 of 5	1		ENSP00000468578.1	K7ES70
MFAP4	ENST00000395592.6 link	c.142G>C	p.Gly48Arg	missense_variant	Exon 2 of 6	1		ENSP00000378957.2	P55083-2
MFAP4	ENST00000571210.1 link	n.105G>C		non_coding_transcript_exon_variant	Exon 2 of 5	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.03e-7

AC:

AN:

1422688

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

703876

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.16e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Uncertain

0.012

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

0.56

LIST_S2

Benign

0.71

T;T;T

M_CAP

Benign

0.024

MetaRNN

Benign

0.13

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

.;.;N

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-0.030

.;N;N

REVEL

Benign

0.082

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

0.13

MPC

0.53

ClinPred

0.27

GERP RS

3.9

Varity_R

0.080

gMVP

0.64

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over