13-98450353-C-T

Position:

• chr13-98450353-C-T

Variant summary

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

The ENST00000319562.11(FARP1):​c.*2036C>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 0.26 in 152,160 control chromosomes in the GnomAD database, including 5,285 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 0.26 (5283 hom., cov: 33)
  • Exomes 𝑓: 0.67 (2 hom.)
• Consequence: FARP1 ENST00000319562.11 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17

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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.295 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STK24	NM_001032296.4	c.*2820G>A		3_prime_UTR_variant	11/11	ENST00000539966.6	NP_001027467.2
FARP1	NM_005766.4	c.*2036C>T		3_prime_UTR_variant	27/27	ENST00000319562.11	NP_005757.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FARP1	ENST00000319562.11	c.*2036C>T		3_prime_UTR_variant	27/27	1	NM_005766.4	ENSP00000322926	P1
STK24	ENST00000539966.6	c.*2820G>A		3_prime_UTR_variant	11/11	1	NM_001032296.4	ENSP00000442539	P1
STK24	ENST00000376554.8	c.*2820G>A		3_prime_UTR_variant	5/5	5		ENSP00000365737
STK24	ENST00000397517.6	c.*2820G>A		3_prime_UTR_variant	10/10	2		ENSP00000380651

Frequencies

GnomAD3 genomes AF: 0.260 AC: 39506 AN: 152036 Hom.: 5272 Cov.: 33

Gnomad AFR AF: 0.226

Gnomad AMI AF: 0.315

Gnomad AMR AF: 0.242

Gnomad ASJ AF: 0.262

Gnomad EAS AF: 0.169

Gnomad SAS AF: 0.230

Gnomad FIN AF: 0.226

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.298

Gnomad OTH AF: 0.260

GnomAD4 exome AF: 0.667 AC: 4 AN: 6 Hom.: 2 Cov.: 0 AF XY: 1.00 AC XY: 4 AN XY: 4

Gnomad4 NFE exome AF: 0.667

GnomAD4 genome AF: 0.260 AC: 39543 AN: 152154 Hom.: 5283 Cov.: 33 AF XY: 0.256 AC XY: 19023 AN XY: 74390

Gnomad4 AFR AF: 0.226

Gnomad4 AMR AF: 0.241

Gnomad4 ASJ AF: 0.262

Gnomad4 EAS AF: 0.169

Gnomad4 SAS AF: 0.230

Gnomad4 FIN AF: 0.226

Gnomad4 NFE AF: 0.298

Gnomad4 OTH AF: 0.259

Alfa AF: 0.249 Hom.: 1923

Bravo AF: 0.257

Asia WGS AF: 0.199 AC: 694 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.10
DANN	Benign	0.34

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: rs3742136; hg19: chr13-99102607;