chr1-16976710-G-A

Variant summary

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

The NM_002403.4(MFAP2):​c.239C>T​(p.Pro80Leu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

MFAP2
NM_002403.4 missense, splice_region

Scores

19
Splicing: ADA: 0.007319
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.38
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]

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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=0.02726838).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MFAP2NM_002403.4 linkuse as main transcriptc.239C>T p.Pro80Leu missense_variant, splice_region_variant 5/9 ENST00000375535.4
LOC105376806XR_947003.3 linkuse as main transcriptn.702+148G>A intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MFAP2ENST00000375535.4 linkuse as main transcriptc.239C>T p.Pro80Leu missense_variant, splice_region_variant 5/91 NM_002403.4 A1P55001-1
ENST00000654887.1 linkuse as main transcriptn.261+148G>A intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32

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 submitterclinical testingAmbry GeneticsDec 27, 2022The c.239C>T (p.P80L) alteration is located in exon 5 (coding exon 4) of the MFAP2 gene. This alteration results from a C to T substitution at nucleotide position 239, causing the proline (P) at amino acid position 80 to be replaced by a leucine (L). 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
0.062
BayesDel_addAF
Benign
-0.24
T
BayesDel_noAF
Benign
-0.59
CADD
Benign
21
DANN
Benign
0.87
DEOGEN2
Benign
0.31
.;T
Eigen
Benign
-1.0
Eigen_PC
Benign
-0.92
FATHMM_MKL
Benign
0.11
N
LIST_S2
Benign
0.67
T;T
M_CAP
Benign
0.0033
T
MetaRNN
Benign
0.027
T;T
MetaSVM
Benign
-0.94
T
MutationAssessor
Benign
0.75
.;N
MutationTaster
Benign
0.95
D;D;D
PrimateAI
Benign
0.28
T
PROVEAN
Benign
0.080
N;N
REVEL
Benign
0.023
Sift
Benign
0.54
T;T
Sift4G
Benign
0.55
T;T
Polyphen
0.0
.;B
Vest4
0.057
MutPred
0.33
.;Gain of catalytic residue at P80 (P = 0.0516);
MVP
0.055
MPC
0.31
ClinPred
0.039
T
GERP RS
0.28
Varity_R
0.017
gMVP
0.13

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.0073
dbscSNV1_RF
Benign
0.30
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-17303205; API