12-8648103-G-T

Variant names:

• chr12-8648103-G-T
• NM_003480.4:c.510C>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_003480.4(MFAP5):​c.510C>A​(p.Pro170Pro) variant causes a synonymous 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. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MFAP5 NM_003480.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.168
• Publications: 0 publications found

Genes affected

MFAP5 (HGNC:29673): (microfibril associated protein 5) This gene encodes a 25-kD microfibril-associated glycoprotein which is a component of microfibrils of the extracellular matrix. The encoded protein promotes attachment of cells to microfibrils via alpha-V-beta-3 integrin. Deficiency of this gene in mice results in neutropenia. Alternate splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2014]

MFAP5 Gene-Disease associations (from GenCC):

• aortic aneurysm, familial thoracic 9

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• familial thoracic aortic aneurysm and aortic dissection

  Inheritance: AD, Unknown Classification: MODERATE, SUPPORTIVE Submitted by: Orphanet, ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.074).
• BP6: Variant 12-8648103-G-T is Benign according to our data. Variant chr12-8648103-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3395453.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.168 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003480.4. 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
	MFAP5	NM_003480.4	MANE Select	c.510C>A	p.Pro170Pro	synonymous	Exon 10 of 10	NP_003471.1	Q13361-1
	MFAP5	NM_001297709.2		c.480C>A	p.Pro160Pro	synonymous	Exon 9 of 9	NP_001284638.1	Q13361-2
	MFAP5	NM_001297710.2		c.444C>A	p.Pro148Pro	synonymous	Exon 8 of 8	NP_001284639.1	F5GYX4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MFAP5	ENST00000359478.7	TSL:1 MANE Select	c.510C>A	p.Pro170Pro	synonymous	Exon 10 of 10	ENSP00000352455.2	Q13361-1
	MFAP5	ENST00000856658.1		c.567C>A	p.Pro189Pro	synonymous	Exon 10 of 10	ENSP00000526717.1
	MFAP5	ENST00000856657.1		c.510C>A	p.Pro170Pro	synonymous	Exon 11 of 11	ENSP00000526716.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Cardiovascular phenotype (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.2
DANN	Benign	0.24
PhyloP100		0.17

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

Other links and lift over

hg19: chr12-8800699;