rs778015208

Variant names:

• chr13-98448277-G-A
• rs778015208
• NM_005766.4:c.3098G>A

Your query was ambiguous. Multiple possible variants found:

• chr13-98448277-G-A
• chr13-98448277-G-C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_005766.4(FARP1):​c.3098G>A​(p.Arg1033Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000254 in 1,614,024 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000025 (0 hom.)
• Consequence: FARP1 NM_005766.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.91
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31946623).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005766.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FARP1	NM_005766.4	MANE Select	c.3098G>A	p.Arg1033Gln	missense	Exon 27 of 27	NP_005757.1	A0A2X0TVY0
	STK24	NM_001032296.4	MANE Select	c.*4896C>T		3_prime_UTR	Exon 11 of 11	NP_001027467.2	Q9Y6E0-2
	FARP1	NM_001286839.2		c.3191G>A	p.Arg1064Gln	missense	Exon 28 of 28	NP_001273768.1	C9JME2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FARP1	ENST00000319562.11	TSL:1 MANE Select	c.3098G>A	p.Arg1033Gln	missense	Exon 27 of 27	ENSP00000322926.6	Q9Y4F1-1
	FARP1	ENST00000595437.5	TSL:1	c.3191G>A	p.Arg1064Gln	missense	Exon 28 of 28	ENSP00000471242.1	C9JME2
	STK24	ENST00000539966.6	TSL:1 MANE Select	c.*4896C>T		3_prime_UTR	Exon 11 of 11	ENSP00000442539.2	Q9Y6E0-2

Frequencies

GnomAD3 genomes AF: 0.0000328 AC: 5 AN: 152212 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000119 AC: 3 AN: 251472 AF XY: 0.0000147

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000246 AC: 36 AN: 1461812 Hom.: 0 Cov.: 31 AF XY: 0.0000220 AC XY: 16 AN XY: 727218

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39698

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.0000297 AC: 33 AN: 1111960

Other (OTH) AF: 0.00 AC: 0 AN: 60388

GnomAD4 genome AF: 0.0000328 AC: 5 AN: 152212 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74370

African (AFR) AF: 0.0000241 AC: 1 AN: 41448

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000434 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.00000824 AC: 1

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.094	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.012	T
Eigen	Benign	0.041
Eigen_PC	Benign	-0.076
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.83	T
M_CAP	Uncertain	0.15	D
MetaRNN	Benign	0.32	T
MetaSVM	Uncertain	0.071	D
MutationAssessor	Uncertain	2.7	M
PhyloP100		4.9
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-2.2	N
REVEL	Uncertain	0.39
Sift	Benign	0.053	T
Sift4G	Benign	0.099	T
Polyphen		0.97	D
Vest4		0.14
MutPred		0.28		Gain of catalytic residue at L1068 (P = 0.0047)
MVP		0.81
MPC		0.27
ClinPred		0.72	D
GERP RS		4.3
Varity_R		0.10
gMVP		0.37
Mutation Taster		=91/9	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs778015208; hg19: chr13-99100531;