rs1554401762

Variant names:

• chr7-128856570-G-GTGCCCGGGGCGTGATTGA
• rs1554401762
• NM_001458.5:c.7313_7330dupGCGTGATTGATGCCCGGG

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM4

The NM_001458.5(FLNC):​c.7313_7330dupGCGTGATTGATGCCCGGG​(p.Gly2438_Arg2443dup) variant causes a disruptive inframe insertion change involving the alteration of a non-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 INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. V2444V) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: FLNC NM_001458.5 disruptive_inframe_insertion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.41
• Publications: 0 publications found

Genes affected

FLNC (HGNC:3756): (filamin C) This gene encodes one of three related filamin genes, specifically gamma filamin. These filamin proteins crosslink actin filaments into orthogonal networks in cortical cytoplasm and participate in the anchoring of membrane proteins for the actin cytoskeleton. Three functional domains exist in filamin: an N-terminal filamentous actin-binding domain, a C-terminal self-association domain, and a membrane glycoprotein-binding domain. Mutations in this gene are a cause of cardiopathy. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2022]

FLNC-AS1 (HGNC:53474): (FLNC antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_001458.5.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001458.5. 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
	FLNC	NM_001458.5	MANE Select	c.7313_7330dupGCGTGATTGATGCCCGGG	p.Gly2438_Arg2443dup	disruptive_inframe_insertion	Exon 44 of 48	NP_001449.3	Q14315-1
	FLNC	NM_001127487.2		c.7214_7231dupGCGTGATTGATGCCCGGG	p.Gly2405_Arg2410dup	disruptive_inframe_insertion	Exon 43 of 47	NP_001120959.1	Q14315-2
	FLNC-AS1	NR_149055.1		n.103-3191_103-3174dupTCAATCACGCCCCGGGCA		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLNC	ENST00000325888.13	TSL:1 MANE Select	c.7313_7330dupGCGTGATTGATGCCCGGG	p.Gly2438_Arg2443dup	disruptive_inframe_insertion	Exon 44 of 48	ENSP00000327145.8	Q14315-1
	FLNC	ENST00000346177.6	TSL:1	c.7214_7231dupGCGTGATTGATGCCCGGG	p.Gly2405_Arg2410dup	disruptive_inframe_insertion	Exon 43 of 47	ENSP00000344002.6	Q14315-2
	FLNC	ENST00000950263.1		c.7211_7228dupGCGTGATTGATGCCCGGG	p.Gly2404_Arg2409dup	disruptive_inframe_insertion	Exon 43 of 47	ENSP00000620322.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Myofibrillar myopathy 5;C3279722:Distal myopathy with posterior leg and anterior hand involvement;C4310749:Hypertrophic cardiomyopathy 26;na:Dilated Cardiomyopathy, Dominant (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.4

Splicing

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

Other links and lift over

dbSNP: rs1554401762; hg19: chr7-128496624;