Variant 5-154049736-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.14G>A(p.Cys5Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000185 in 1,612,494 control chromosomes in the GnomAD database, including 1 homozygotes. 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 0.00021 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00018 ( 1 hom. )

Consequence

MFAP3
NM_005927.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0860

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:

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=0.013384432).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MFAP3	NM_005927.5 linkuse as main transcript	c.14G>A	p.Cys5Tyr	missense_variant	2/3	ENST00000522782.6	NP_005918.1
MFAP3	NM_001242336.2 linkuse as main transcript	c.14G>A	p.Cys5Tyr	missense_variant	2/3		NP_001229265.1
MFAP3	NM_001135037.2 linkuse as main transcript	c.-143-3184G>A		intron_variant			NP_001128509.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MFAP3	ENST00000522782.6 linkuse as main transcript	c.14G>A	p.Cys5Tyr	missense_variant	2/3	1	NM_005927.5	ENSP00000430852	P1	P55082-1

Frequencies

GnomAD3 genomes

AF:

0.000210

AC:

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00111

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:

0.000221

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000311

AC:

AN:

250496

Hom.:

AF XY:

0.000303

AC XY:

AN XY:

135398

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00165

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:

0.000159

Gnomad OTH exome

AF:

0.000494

GnomAD4 exome

AF:

0.000183

AC:

267

AN:

1460196

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

127

AN XY:

726234

show subpopulations

Gnomad4 AFR exome

AF:

0.0000898

Gnomad4 AMR exome

AF:

0.00170

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:

0.000150

Gnomad4 OTH exome

AF:

0.000348

GnomAD4 genome

AF:

0.000210

AC:

AN:

152298

Hom.:

Cov.:

AF XY:

0.000228

AC XY:

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00111

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000221

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000171

Hom.:

Bravo

AF:

0.000438

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000247

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.000237

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

Aug 01, 2022

The c.14G>A (p.C5Y) 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 14, causing the cysteine (C) at amino acid position 5 to be replaced by a tyrosine (Y). 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

0.058

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.62

CADD

Benign

6.5

DANN

Benign

0.27

DEOGEN2

Benign

0.054

T;T;T;.

Eigen

Benign

-0.95

Eigen_PC

Benign

-0.77

FATHMM_MKL

Benign

0.057

LIST_S2

Benign

0.57

T;T;T;.

M_CAP

Benign

0.0036

MetaRNN

Benign

0.013

T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.0

.;N;.;.

MutationTaster

Benign

0.99

D;N;N

PrimateAI

Benign

0.25

PROVEAN

Benign

1.0

N;N;N;D

REVEL

Benign

0.056

Sift

Benign

1.0

T;T;T;.

Sift4G

Benign

1.0

T;T;T;.

Polyphen

0.0

.;B;.;.

Vest4

0.10

MVP

0.30

ClinPred

0.013

GERP RS

2.6

Varity_R

0.030

gMVP

0.53

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