chr13-98448268-C-T

Position:

• chr13-98448268-C-T

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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.06

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]

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]

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/exons	MANE	UniProt
FARP1	NM_005766.4	c.3089C>T	p.Ser1030Phe	missense_variant	27/27	ENST00000319562.11
STK24	NM_001032296.4	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	c.3089C>T	p.Ser1030Phe	missense_variant	27/27	1	NM_005766.4	P1
FARP1	ENST00000595437.5	c.3182C>T	p.Ser1061Phe	missense_variant	28/28	1
STK24	ENST00000539966.6	c.*4905G>A		3_prime_UTR_variant	11/11	1	NM_001032296.4	P1
FARP1	ENST00000627049.2	c.3182C>T	p.Ser1061Phe	missense_variant	28/28	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461792 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727200

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.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

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	D
BayesDel_noAF	Benign	-0.12
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	.;.;T
Eigen	Benign	0.047
Eigen_PC	Benign	0.0014
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.94	.;D;D
M_CAP	Uncertain	0.22	D
MetaRNN	Uncertain	0.48	T;T;T
MetaSVM	Uncertain	0.22	D
MutationAssessor	Uncertain	2.5	.;.;M
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-4.1	.;.;D
REVEL	Uncertain	0.45
Sift	Uncertain	0.0010	.;.;D
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	D
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.

Other links and lift over

hg19: chr13-99100522;