NM_002403.4:c.432T>A

Variant names:

• chr1-16975285-A-T
• rs761422
• NM_002403.4:c.432T>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_002403.4(MFAP2):​c.432T>A​(p.His144Gln) variant causes a missense 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: MFAP2 NM_002403.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.372
• Publications: 40 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33598992).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002403.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MFAP2	NM_002403.4	MANE Select	c.432T>A	p.His144Gln	missense	Exon 8 of 9	NP_002394.1	P55001-1
	MFAP2	NM_017459.3		c.432T>A	p.His144Gln	missense	Exon 8 of 9	NP_059453.1	P55001-1
	MFAP2	NM_001135247.2		c.429T>A	p.His143Gln	missense	Exon 8 of 9	NP_001128719.1	P55001-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MFAP2	ENST00000375535.4	TSL:1 MANE Select	c.432T>A	p.His144Gln	missense	Exon 8 of 9	ENSP00000364685.3	P55001-1
	MFAP2	ENST00000930335.1		c.522T>A	p.His174Gln	missense	Exon 9 of 10	ENSP00000600394.1
	MFAP2	ENST00000930331.1		c.495T>A	p.His165Gln	missense	Exon 8 of 9	ENSP00000600390.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 50

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 46709

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Uncertain	0.094	D
BayesDel_noAF	Benign	-0.10
CADD	Benign	3.2
DANN	Benign	0.87
DEOGEN2	Benign	0.41	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.34	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		-0.37
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-0.090	N
REVEL	Uncertain	0.33
Sift	Benign	0.078	T
Sift4G	Benign	0.11	T
Polyphen		0.0010	B
Vest4		0.50
MutPred		0.41		Gain of relative solvent accessibility (P = 0.2363)
MVP		0.081
MPC		0.32
ClinPred		0.48	T
GERP RS		-4.4
Varity_R		0.19
gMVP		0.36
Mutation Taster		=55/45	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs761422; hg19: chr1-17301780;