15-43874206-GG-AA

Variant names:

• chr15-43874206-GG-AA
• NM_032892.5:c.1391_1392delCCinsTT
• FRMD5 p.Ala464Val

Variant summary

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

The NM_032892.5(FRMD5):​c.1391_1392delCCinsTT​(p.Ala464Val) 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: 32)
• Consequence: FRMD5 NM_032892.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.00
• Publications: 0 publications found

Genes affected

FRMD5 (HGNC:28214): (FERM domain containing 5) Enables integrin binding activity and protein kinase binding activity. Involved in negative regulation of cell motility; positive regulation of cell adhesion; and regulation of cell migration. Located in adherens junction. [provided by Alliance of Genome Resources, Apr 2022]

FRMD5 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with eye movement abnormalities and ataxia

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032892.5. 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
	FRMD5	NM_032892.5	MANE Select	c.1391_1392delCCinsTT	p.Ala464Val	missense	N/A	NP_116281.2	Q7Z6J6-1
	FRMD5	NM_001411124.1		c.1391_1392delCCinsTT	p.Ala464Val	missense	N/A	NP_001398053.1	B5MC67
	FRMD5	NM_001322949.2		c.1391_1392delCCinsTT	p.Ala464Val	missense	N/A	NP_001309878.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FRMD5	ENST00000417257.6	TSL:1 MANE Select	c.1391_1392delCCinsTT	p.Ala464Val	missense	N/A	ENSP00000403067.1	Q7Z6J6-1
	FRMD5	ENST00000421674.5	TSL:1	n.*1335_*1336delCCinsTT		non_coding_transcript_exon	Exon 15 of 15	ENSP00000401635.1	F8WEJ8
	FRMD5	ENST00000458630.5	TSL:1	n.*1338_*1339delCCinsTT		non_coding_transcript_exon	Exon 15 of 15	ENSP00000404496.1	H7C282

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		4.0

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: chr15-44166404;