rs112180788

Variant names:

• chr7-128858364-C-A
• rs112180788
• NM_001458.5:c.8019C>A

Your query was ambiguous. Multiple possible variants found:

• chr7-128858364-C-A
• chr7-128858364-C-G
• chr7-128858364-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001458.5(FLNC):​c.8019C>A​(p.His2673Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. Synonymous variant affecting the same amino acid position (i.e. H2673H) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FLNC NM_001458.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.12
• Publications: 1 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.

• PM2: Very rare variant in population databases, with high coverage

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLNC	NM_001458.5	MANE Select	c.8019C>A	p.His2673Gln	missense	Exon 48 of 48	NP_001449.3
	FLNC	NM_001127487.2		c.7920C>A	p.His2640Gln	missense	Exon 47 of 47	NP_001120959.1
	FLNC-AS1	NR_149055.1		n.102+4161G>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLNC	ENST00000325888.13	TSL:1 MANE Select	c.8019C>A	p.His2673Gln	missense	Exon 48 of 48	ENSP00000327145.8
	FLNC	ENST00000346177.6	TSL:1	c.7920C>A	p.His2640Gln	missense	Exon 47 of 47	ENSP00000344002.6
	FLNC	ENST00000714183.1		c.7881C>A	p.His2627Gln	missense	Exon 47 of 47	ENSP00000519472.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 26

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.78
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Benign	0.072
DANN	Benign	0.88
DEOGEN2	Uncertain	0.75	D
Eigen	Benign	-0.92
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.15	N
LIST_S2	Uncertain	0.87	D
M_CAP	Uncertain	0.22	D
MetaRNN	Uncertain	0.68	D
MetaSVM	Uncertain	-0.060	T
MutationAssessor	Benign	1.3	L
PhyloP100		-3.1
PrimateAI	Uncertain	0.77	T
PROVEAN	Uncertain	-3.8	D
REVEL	Uncertain	0.54
Sift	Uncertain	0.011	D
Sift4G	Benign	0.17	T
Polyphen		1.0	D
Vest4		0.68
MutPred		0.42		Gain of loop (P = 0.1069)
MVP		0.87
MPC		1.6
ClinPred		0.97	D
GERP RS		-5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.82
gMVP		0.62
Mutation Taster		=31/69	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

dbSNP: rs112180788; hg19: chr7-128498418;