20-14326061-CA-TC

Variant names:

• chr20-14326061-CA-TC
• NM_198391.3:c.1445_1446delTGinsGA
• FLRT3 p.Met482Arg

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_198391.3(FLRT3):​c.1445_1446delTGinsGA​(p.Met482Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M482K) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FLRT3 NM_198391.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.32
• Publications: 0 publications found

Genes affected

FLRT3 (HGNC:3762): (fibronectin leucine rich transmembrane protein 3) This gene encodes a member of the fibronectin leucine rich transmembrane protein (FLRT) family. FLRTs may function in cell adhesion and/or receptor signalling. Their protein structures resemble small leucine-rich proteoglycans found in the extracellular matrix. This gene is expressed in many tissues. Two alternatively spliced transcript variants encoding the same protein have been described for this gene. [provided by RefSeq, Jul 2010]

MACROD2 (HGNC:16126): (mono-ADP ribosylhydrolase 2) The protein encoded by this gene is a deacetylase involved in removing ADP-ribose from mono-ADP-ribosylated proteins. The encoded protein has been shown to translocate from the nucleus to the cytoplasm upon DNA damage. [provided by RefSeq, May 2017]

ACMG classification

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

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198391.3. 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
	FLRT3	NM_198391.3	MANE Select	c.1445_1446delTGinsGA	p.Met482Arg	missense	N/A	NP_938205.1	Q9NZU0
	MACROD2	NM_001351661.2	MANE Select	c.272-167418_272-167417delCAinsTC		intron	N/A	NP_001338590.1	A1Z1Q3-1
	FLRT3	NM_013281.4		c.1445_1446delTGinsGA	p.Met482Arg	missense	N/A	NP_037413.1	Q9NZU0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLRT3	ENST00000341420.5	TSL:2 MANE Select	c.1445_1446delTGinsGA	p.Met482Arg	missense	N/A	ENSP00000339912.4	Q9NZU0
	FLRT3	ENST00000378053.3	TSL:1	c.1445_1446delTGinsGA	p.Met482Arg	missense	N/A	ENSP00000367292.3	Q9NZU0
	MACROD2	ENST00000684519.1	MANE Select	c.272-167418_272-167417delCAinsTC		intron	N/A	ENSP00000507484.1	A1Z1Q3-1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		9.3

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr20-14306707;