dbSNP rs201874534: MFAP2:p.Ala174Val (chr1-16974951-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_002403.4(MFAP2):c.521C>T(p.Ala174Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/20 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. A174G) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0000070 ( 0 hom., cov: 17)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MFAP2
NM_002403.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.48

Variant links:

Genes affected

MFAP2 (HGNC:7033): (microfibril associated protein 2) Microfibrillar-associated protein 2 is a major antigen of elastin-associated microfibrils and a candidate for involvement in the etiology of inherited connective tissue diseases. Four transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Sep 2008]

MFAP2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.10219082).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MFAP2	NM_002403.4 link	c.521C>T	p.Ala174Val	missense_variant	Exon 9 of 9	ENST00000375535.4	NP_002394.1	P55001-1A0A024RA94

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MFAP2	ENST00000375535.4 link	c.521C>T	p.Ala174Val	missense_variant	Exon 9 of 9	1	NM_002403.4	ENSP00000364685.3	P55001-1
MFAP2	ENST00000375534.7 link	c.518C>T	p.Ala173Val	missense_variant	Exon 8 of 8	2		ENSP00000364684.3	P55001-2
MFAP2	ENST00000490075.5 link	n.1922C>T		non_coding_transcript_exon_variant	Exon 6 of 6	2

Frequencies

GnomAD3 genomes

AF:

0.00000698

AC:

AN:

143210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000152

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

836010

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

429320

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000698

AC:

AN:

143210

Hom.:

Cov.:

AF XY:

0.0000144

AC XY:

AN XY:

69226

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000152

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.078

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.24

.;T

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.30

FATHMM_MKL

Benign

0.45

LIST_S2

Benign

0.80

T;T

M_CAP

Benign

0.0035

MetaRNN

Benign

0.10

T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.34

.;N

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.48

N;N

REVEL

Benign

0.14

Sift

Uncertain

0.0060

D;D

Sift4G

Uncertain

0.044

D;D

Polyphen

0.30

.;B

Vest4

0.17

MutPred

0.51

.;Gain of relative solvent accessibility (P = 0.09);

MVP

0.13

MPC

0.31

ClinPred

0.58

GERP RS

3.0

Varity_R

0.083

gMVP

0.38

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over