11-64117358-GG-AA

Variant names:

• chr11-64117358-GG-AA
• NM_013280.5:c.1091_1092delGGinsAA
• FLRT1 p.Arg364Gln

Variant summary

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

The NM_013280.5(FLRT1):​c.1091_1092delGGinsAA​(p.Arg364Gln) variant causes a missense change. 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 34)
• Consequence: FLRT1 NM_013280.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.74
• Publications: 0 publications found

Genes affected

FLRT1 (HGNC:3760): (fibronectin leucine rich transmembrane protein 1) This gene encodes a member of the fibronectin leucine rich transmembrane protein (FLRT) family. The family members may function in cell adhesion and/or receptor signalling. Their protein structures resemble small leucine-rich proteoglycans found in the extracellular matrix. The encoded protein shares sequence similarity with two other family members, FLRT2 and FLRT3. This gene is expressed in kidney and brain. [provided by RefSeq, Jul 2008]

MACROD1 (HGNC:29598): (mono-ADP ribosylhydrolase 1) Enables ADP-ribosylglutamate hydrolase activity and deacetylase activity. Involved in cellular response to DNA damage stimulus; peptidyl-glutamate ADP-deribosylation; and purine nucleoside metabolic process. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013280.5. 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
	FLRT1	NM_013280.5	MANE Select	c.1091_1092delGGinsAA	p.Arg364Gln	missense	N/A	NP_037412.2
	MACROD1	NM_014067.4	MANE Select	c.517+33880_517+33881delCCinsTT		intron	N/A	NP_054786.2
	FLRT1	NM_001384466.1		c.1091_1092delGGinsAA	p.Arg364Gln	missense	N/A	NP_001371395.1	Q9NZU1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLRT1	ENST00000682287.1	MANE Select	c.1091_1092delGGinsAA	p.Arg364Gln	missense	N/A	ENSP00000507207.1	Q9NZU1-2
	FLRT1	ENST00000246841.3	TSL:1	c.1091_1092delGGinsAA	p.Arg364Gln	missense	N/A	ENSP00000246841.3	Q9NZU1-2
	MACROD1	ENST00000255681.7	TSL:1 MANE Select	c.517+33880_517+33881delCCinsTT		intron	N/A	ENSP00000255681.6	Q9BQ69

Frequencies

GnomAD3 genomes Cov.: 34

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

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.7

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: chr11-63884830;