13-98451916-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005766.4(FARP1):c.*3599C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 152,036 control chromosomes in the GnomAD database, including 3,637 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.21 (3635 hom., cov: 32)
  • Exomes 𝑓: 0.19 (2 hom.)
• Consequence: FARP1 NM_005766.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.29

Genes affected

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]

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.238 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STK24	NM_001032296.4	c.*1257G>A		3_prime_UTR_variant	11/11	ENST00000539966.6
FARP1	NM_005766.4	c.*3599C>T		3_prime_UTR_variant	27/27	ENST00000319562.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FARP1	ENST00000319562.11	c.*3599C>T		3_prime_UTR_variant	27/27	1	NM_005766.4	P1
STK24	ENST00000539966.6	c.*1257G>A		3_prime_UTR_variant	11/11	1	NM_001032296.4	P1
STK24	ENST00000376554.8	c.*1257G>A		3_prime_UTR_variant	5/5	5
STK24	ENST00000397517.6	c.*1257G>A		3_prime_UTR_variant	10/10	2

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32601 AN: 151846 Hom.: 3629 Cov.: 32

Gnomad AFR AF: 0.242

Gnomad AMI AF: 0.197

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.142

Gnomad SAS AF: 0.212

Gnomad FIN AF: 0.168

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.214

GnomAD4 exome AF: 0.194 AC: 14 AN: 72 Hom.: 2 Cov.: 0 AF XY: 0.250 AC XY: 11 AN XY: 44

Gnomad4 AFR exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.219

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.215 AC: 32628 AN: 151964 Hom.: 3635 Cov.: 32 AF XY: 0.211 AC XY: 15646 AN XY: 74290

Gnomad4 AFR AF: 0.242

Gnomad4 AMR AF: 0.183

Gnomad4 ASJ AF: 0.234

Gnomad4 EAS AF: 0.142

Gnomad4 SAS AF: 0.212

Gnomad4 FIN AF: 0.168

Gnomad4 NFE AF: 0.217

Gnomad4 OTH AF: 0.217

Alfa AF: 0.212 Hom.: 3832

Bravo AF: 0.215

Asia WGS AF: 0.191 AC: 664 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.57
Dann	Benign	0.66

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: rs3742134; hg19: chr13-99104170;