13-98435584-G-C

Variant names:

• chr13-98435584-G-C
• rs1892225845
• NM_005766.4:c.2152G>C

Variant summary

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

The NM_005766.4(FARP1):​c.2152G>C​(p.Ala718Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: FARP1 NM_005766.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.50

Genes affected

FARP1 (HGNC:3591): (FERM, ARH/RhoGEF and pleckstrin domain protein 1) This gene encodes a protein containing a FERM (4.2, exrin, radixin, moesin) domain, a Dbl homology domain, and two pleckstrin homology domains. These domains are found in guanine nucleotide exchange factors and proteins that link the cytoskeleton to the cell membrane. The encoded protein functions in neurons to promote dendritic growth. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2013]

FARP1-AS1 (HGNC:40229): (FARP1 antisense RNA 1)

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
FARP1	NM_005766.4	c.2152G>C	p.Ala718Pro	missense_variant	Exon 19 of 27	ENST00000319562.11	NP_005757.1
FARP1	NM_001286839.2	c.2152G>C	p.Ala718Pro	missense_variant	Exon 19 of 28		NP_001273768.1
FARP1-AS1	NR_046595.1	n.144C>G		non_coding_transcript_exon_variant	Exon 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FARP1	ENST00000319562.11	c.2152G>C	p.Ala718Pro	missense_variant	Exon 19 of 27	1	NM_005766.4	ENSP00000322926.6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 06, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2152G>C (p.A718P) alteration is located in exon 19 (coding exon 18) of the FARP1 gene. This alteration results from a G to C substitution at nucleotide position 2152, causing the alanine (A) at amino acid position 718 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.95
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.20
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.075	.;.;T;T
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.92	.;D;D;D
M_CAP	Benign	0.023	T
MetaRNN	Uncertain	0.73	D;D;D;D
MetaSVM	Benign	-0.46	T
MutationAssessor	Uncertain	2.6	.;.;M;.
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-1.9	.;.;N;.
REVEL	Uncertain	0.38
Sift	Benign	0.19	.;.;T;.
Sift4G	Benign	0.20	T;T;T;D
Polyphen		1.0	D;D;D;.
Vest4		0.75
MutPred		0.58		Gain of catalytic residue at M723 (P = 2e-04);Gain of catalytic residue at M723 (P = 2e-04);Gain of catalytic residue at M723 (P = 2e-04);.;
MVP		0.81
MPC		0.98
ClinPred		0.92	D
GERP RS		5.8
Varity_R		0.91
gMVP		0.74

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: rs1892225845; hg19: chr13-99087838;