Variant 5-154049927-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_005927.5(MFAP3):c.205G>A(p.Val69Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000101 in 1,613,590 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00041 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000068 ( 0 hom. )

Consequence

MFAP3
NM_005927.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.962

Variant links:

Genes affected

MFAP3 (HGNC:7034): (microfibril associated protein 3) Predicted to be located in extracellular region. Predicted to be active in cytoplasm; nucleus; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

MFAP3 links:

MFAP3 (HGNC:):

MFAP3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.011150658).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MFAP3	NM_005927.5 linkuse as main transcript	c.205G>A	p.Val69Ile	missense_variant	2/3	ENST00000522782.6	NP_005918.1	P55082-1
MFAP3	NM_001242336.2 linkuse as main transcript	c.205G>A	p.Val69Ile	missense_variant	2/3		NP_001229265.1	P55082-1
MFAP3	NM_001135037.2 linkuse as main transcript	c.-143-2993G>A		intron_variant			NP_001128509.1	P55082-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MFAP3	ENST00000522782.6 linkuse as main transcript	c.205G>A	p.Val69Ile	missense_variant	2/3	1	NM_005927.5	ENSP00000430852.2		P55082-1E5RHQ6

Frequencies

GnomAD3 genomes

AF:

0.000414

AC:

AN:

152126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00142

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.00

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.000151

AC:

AN:

250924

Hom.:

AF XY:

0.000103

AC XY:

AN XY:

135604

show subpopulations

Gnomad AFR exome

AF:

0.00185

Gnomad AMR exome

AF:

0.000145

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:

0.0000265

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000684

AC:

100

AN:

1461346

Hom.:

Cov.:

AF XY:

0.0000729

AC XY:

AN XY:

726984

show subpopulations

Gnomad4 AFR exome

AF:

0.00149

Gnomad4 AMR exome

AF:

0.000134

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000333

Gnomad4 OTH exome

AF:

0.0000828

GnomAD4 genome

AF:

0.000414

AC:

AN:

152244

Hom.:

Cov.:

AF XY:

0.000416

AC XY:

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.00142

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.000157

Hom.:

Bravo

AF:

0.000552

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000181

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Apr 13, 2022

The c.205G>A (p.V69I) alteration is located in exon 2 (coding exon 1) of the MFAP3 gene. This alteration results from a G to A substitution at nucleotide position 205, causing the valine (V) at amino acid position 69 to be replaced by an isoleucine (I). 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

0.077

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.073

T;T;T

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.067

FATHMM_MKL

Benign

0.72

LIST_S2

Benign

0.63

T;T;T

M_CAP

Benign

0.0041

MetaRNN

Benign

0.011

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.3

.;L;.

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.66

N;N;N

REVEL

Benign

0.036

Sift

Benign

0.27

T;T;T

Sift4G

Benign

0.43

T;T;T

Polyphen

0.0090

.;B;.

Vest4

0.081

MVP

0.35

ClinPred

0.0095

GERP RS

4.1

Varity_R

0.062

gMVP

0.40

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over