Variant 13-98448268-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_005766.4(FARP1):c.3089C>T(p.Ser1030Phe) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,792 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

FARP1
NM_005766.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.06

Variant links:

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 links:

STK24 (HGNC:11403): (serine/threonine kinase 24) This gene encodes a serine/threonine protein kinase that functions upstream of mitogen-activated protein kinase (MAPK) signaling. The encoded protein is cleaved into two chains by caspases; the N-terminal fragment (MST3/N) translocates to the nucleus and promotes programmed cells death. There is a pseudogene for this gene on chromosome X. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2013]

STK24 links:

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ACMG classification

Classification made for transcript

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/exons	MANE	UniProt
FARP1	NM_005766.4 linkuse as main transcript	c.3089C>T	p.Ser1030Phe	missense_variant	27/27	ENST00000319562.11
STK24	NM_001032296.4 linkuse as main transcript	c.*4905G>A		3_prime_UTR_variant	11/11	ENST00000539966.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FARP1	ENST00000319562.11 linkuse as main transcript	c.3089C>T	p.Ser1030Phe	missense_variant	27/27	1	NM_005766.4	P1	Q9Y4F1-1
FARP1	ENST00000595437.5 linkuse as main transcript	c.3182C>T	p.Ser1061Phe	missense_variant	28/28	1
STK24	ENST00000539966.6 linkuse as main transcript	c.*4905G>A		3_prime_UTR_variant	11/11	1	NM_001032296.4	P1	Q9Y6E0-2
FARP1	ENST00000627049.2 linkuse as main transcript	c.3182C>T	p.Ser1061Phe	missense_variant	28/28	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461792

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727200

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 23, 2023

The c.3089C>T (p.S1030F) alteration is located in exon 27 (coding exon 26) of the FARP1 gene. This alteration results from a C to T substitution at nucleotide position 3089, causing the serine (S) at amino acid position 1030 to be replaced by a phenylalanine (F). 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

Benign

0.13

BayesDel_addAF

Uncertain

0.085

BayesDel_noAF

Benign

-0.12

Cadd

Benign

Dann

Uncertain

1.0

Eigen

Benign

0.047

Eigen_PC

Benign

0.0014

FATHMM_MKL

Pathogenic

0.98

M_CAP

Uncertain

0.22

MetaRNN

Uncertain

0.48

T;T;T

MetaSVM

Uncertain

0.22

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.49

Sift4G

Uncertain

0.0020

D;D;D

Polyphen

0.86

P;P;P

Vest4

0.33

MutPred

0.35

Gain of catalytic residue at R1064 (P = 0.0021);Gain of catalytic residue at R1064 (P = 0.0021);.;

MVP

0.83

MPC

0.61

ClinPred

0.99

GERP RS

4.3

Varity_R

0.28

gMVP

0.36

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over