rs375986462

Variant names:

• chr7-128846060-C-G
• NM_001458.5:c.3861C>G

Your query was ambiguous. Multiple possible variants found:

• chr7-128846060-C-G
• chr7-128846060-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001458.5(FLNC):​c.3861C>G​(p.His1287Gln) 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.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FLNC NM_001458.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.45

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLNC	NM_001458.5	c.3861C>G	p.His1287Gln	missense_variant	Exon 22 of 48	ENST00000325888.13	NP_001449.3
FLNC	NM_001127487.2	c.3861C>G	p.His1287Gln	missense_variant	Exon 22 of 47		NP_001120959.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FLNC	ENST00000325888.13	c.3861C>G	p.His1287Gln	missense_variant	Exon 22 of 48	1	NM_001458.5	ENSP00000327145.8
FLNC	ENST00000346177.6	c.3861C>G	p.His1287Gln	missense_variant	Exon 22 of 47	1		ENSP00000344002.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Benign	-0.052	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	0.16
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.75	D;.
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.37	N
LIST_S2	Uncertain	0.93	D;D
M_CAP	Benign	0.045	D
MetaRNN	Uncertain	0.64	D;D
MetaSVM	Uncertain	-0.020	T
MutationAssessor	Uncertain	2.3	M;M
PrimateAI	Uncertain	0.68	T
PROVEAN	Pathogenic	-5.1	D;D
REVEL	Uncertain	0.45
Sift	Benign	0.091	T;T
Sift4G	Benign	0.18	T;T
Polyphen		0.88	P;P
Vest4		0.68
MutPred		0.43		Gain of MoRF binding (P = 0.1213);Gain of MoRF binding (P = 0.1213);
MVP		0.52
MPC		0.74
ClinPred		0.99	D
GERP RS		-6.3
Varity_R		0.33
gMVP		0.34

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-128486114;