13-98451063-T-C

Position:

• chr13-98451063-T-C

Variant summary

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

The NM_005766.4(FARP1):​c.*2746T>C 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 152,096 control chromosomes in the GnomAD database, including 5,316 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 (5316 hom., cov: 32)
  • Exomes 𝑓: 0.25 (0 hom.)
• Consequence: FARP1 NM_005766.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.37

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.298 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FARP1	NM_005766.4	c.*2746T>C		3_prime_UTR_variant	27/27	ENST00000319562.11	NP_005757.1
STK24	NM_001032296.4	c.*2110A>G		3_prime_UTR_variant	11/11	ENST00000539966.6	NP_001027467.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FARP1	ENST00000319562.11	c.*2746T>C		3_prime_UTR_variant	27/27	1	NM_005766.4	ENSP00000322926.6
STK24	ENST00000539966	c.*2110A>G		3_prime_UTR_variant	11/11	1	NM_001032296.4	ENSP00000442539.2
STK24	ENST00000397517	c.*2110A>G		3_prime_UTR_variant	10/10	2		ENSP00000380651.3
STK24	ENST00000376554.8	c.*2110A>G		3_prime_UTR_variant	5/5	5		ENSP00000365737.4

Frequencies

GnomAD3 genomes AF: 0.260 AC: 39573 AN: 151970 Hom.: 5306 Cov.: 32

Gnomad AFR AF: 0.224

Gnomad AMI AF: 0.315

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.257

Gnomad EAS AF: 0.154

Gnomad SAS AF: 0.211

Gnomad FIN AF: 0.226

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.302

Gnomad OTH AF: 0.261

GnomAD4 exome AF: 0.250 AC: 2 AN: 8 Hom.: 0 Cov.: 0 AF XY: 0.250 AC XY: 2 AN XY: 8

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.167

GnomAD4 genome AF: 0.260 AC: 39606 AN: 152088 Hom.: 5316 Cov.: 32 AF XY: 0.255 AC XY: 18957 AN XY: 74374

Gnomad4 AFR AF: 0.225

Gnomad4 AMR AF: 0.246

Gnomad4 ASJ AF: 0.257

Gnomad4 EAS AF: 0.154

Gnomad4 SAS AF: 0.212

Gnomad4 FIN AF: 0.226

Gnomad4 NFE AF: 0.302

Gnomad4 OTH AF: 0.260

Alfa AF: 0.283 Hom.: 2399

Bravo AF: 0.259

Asia WGS AF: 0.194 AC: 675 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.24
DANN	Benign	0.23

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: rs7983438; hg19: chr13-99103317;