X-154353120-G-C

Variant names:

• chrX-154353120-G-C
• rs1557176131
• NM_001110556.2:c.6107C>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_001110556.2(FLNA):​c.6107C>G​(p.Pro2036Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 25)
• Consequence: FLNA NM_001110556.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.31

Genes affected

FLNA (HGNC:3754): (filamin A) The protein encoded by this gene is an actin-binding protein that crosslinks actin filaments and links actin filaments to membrane glycoproteins. The encoded protein is involved in remodeling the cytoskeleton to effect changes in cell shape and migration. This protein interacts with integrins, transmembrane receptor complexes, and second messengers. Defects in this gene are a cause of several syndromes, including periventricular nodular heterotopias (PVNH1, PVNH4), otopalatodigital syndromes (OPD1, OPD2), frontometaphyseal dysplasia (FMD), Melnick-Needles syndrome (MNS), and X-linked congenital idiopathic intestinal pseudoobstruction (CIIPX). Two transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Mar 2009]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23339778).
• BP6: Variant X-154353120-G-C is Benign according to our data. Variant chrX-154353120-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 435206.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLNA	NM_001110556.2	c.6107C>G	p.Pro2036Arg	missense_variant	Exon 38 of 48	ENST00000369850.10	NP_001104026.1
FLNA	NM_001456.4	c.6083C>G	p.Pro2028Arg	missense_variant	Exon 37 of 47		NP_001447.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FLNA	ENST00000369850.10	c.6107C>G	p.Pro2036Arg	missense_variant	Exon 38 of 48	1	NM_001110556.2	ENSP00000358866.3

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 25

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Feb 13, 2017

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Uncertain	0.033	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	23
DANN	Benign	0.96
DEOGEN2	Benign	0.30	T;.;.;.;.
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.94	D;D;.;D;D
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.23	T;T;T;T;T
MetaSVM	Uncertain	0.31	D
MutationAssessor	Benign	-1.4	N;.;.;.;.
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	1.3	N;.;N;N;N
REVEL	Uncertain	0.33
Sift	Benign	0.25	T;.;T;T;T
Sift4G	Benign	0.47	T;T;T;T;T
Polyphen		0.0	B;.;B;B;.
Vest4		0.18
MutPred		0.43		Gain of MoRF binding (P = 0.0029);.;.;.;.;
MVP		0.75
MPC		0.54
ClinPred		0.44	T
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.13
gMVP		0.34

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs1557176131; hg19: chrX-153581488;