dbSNP rs12261: FARP1:p.Ser1038Arg (chr13-98448293-T-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_005766.4(FARP1):c.3114T>A(p.Ser1038Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,576 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

FARP1
NM_005766.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.127

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 rank	MANE	Protein	UniProt
FARP1	NM_005766.4 link	c.3114T>A	p.Ser1038Arg	missense_variant	Exon 27 of 27	ENST00000319562.11	NP_005757.1	Q9Y4F1-1A0A2X0TVY0
STK24	NM_001032296.4 link	c.*4880A>T		3_prime_UTR_variant	Exon 11 of 11	ENST00000539966.6	NP_001027467.2	Q9Y6E0-2Q5U0E6Q6P0Y1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
FARP1	ENST00000319562.11 link	c.3114T>A	p.Ser1038Arg	missense_variant	Exon 27 of 27	1	NM_005766.4	ENSP00000322926.6	Q9Y4F1-1
FARP1	ENST00000595437.5 link	c.3207T>A	p.Ser1069Arg	missense_variant	Exon 28 of 28	1		ENSP00000471242.1	C9JME2
STK24	ENST00000539966 link	c.*4880A>T		3_prime_UTR_variant	Exon 11 of 11	1	NM_001032296.4	ENSP00000442539.2	Q9Y6E0-2
FARP1	ENST00000627049.2 link	c.3207T>A	p.Ser1069Arg	missense_variant	Exon 28 of 28	5		ENSP00000486285.1	C9JME2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461576

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727104

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Uncertain

0.078

BayesDel_noAF

Benign

-0.13

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.019

.;.;T

Eigen

Benign

-0.69

Eigen_PC

Benign

-0.72

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.82

.;T;T

M_CAP

Uncertain

0.19

MetaRNN

Uncertain

0.64

D;D;D

MetaSVM

Uncertain

-0.014

MutationAssessor

Uncertain

2.1

.;.;M

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-1.4

.;.;N

REVEL

Uncertain

0.47

Sift

Uncertain

0.011

.;.;D

Sift4G

Uncertain

0.014

D;D;D

Polyphen

0.97

D;D;P

Vest4

0.30

MutPred

0.24

Gain of catalytic residue at R1064 (P = 0.0025);Gain of catalytic residue at R1064 (P = 0.0025);.;

MVP

0.72

MPC

0.42

ClinPred

0.89

GERP RS

1.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.13

gMVP

0.53

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over