chr13-98451750-T-C

Variant names:

• chr13-98451750-T-C
• rs7988959
• NM_005766.4:c.*3433T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005766.4(FARP1):​c.*3433T>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 0.23 in 152,156 control chromosomes in the GnomAD database, including 4,433 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 0.23 (4433 hom., cov: 32)
  • Exomes 𝑓: 0.22 (0 hom.)
• Consequence: FARP1 NM_005766.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.89
• Publications: 5 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.294 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FARP1	NM_005766.4	c.*3433T>C		3_prime_UTR_variant	Exon 27 of 27	ENST00000319562.11	NP_005757.1
STK24	NM_001032296.4	c.*1423A>G		3_prime_UTR_variant	Exon 11 of 11	ENST00000539966.6	NP_001027467.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FARP1	ENST00000319562.11	c.*3433T>C		3_prime_UTR_variant	Exon 27 of 27	1	NM_005766.4	ENSP00000322926.6
STK24	ENST00000539966.6	c.*1423A>G		3_prime_UTR_variant	Exon 11 of 11	1	NM_001032296.4	ENSP00000442539.2
STK24	ENST00000397517.6	c.*1423A>G		3_prime_UTR_variant	Exon 10 of 10	2		ENSP00000380651.3
STK24	ENST00000376554.8	c.*1423A>G		3_prime_UTR_variant	Exon 5 of 5	5		ENSP00000365737.4

Frequencies

GnomAD3 genomes AF: 0.230 AC: 34909 AN: 152006 Hom.: 4431 Cov.: 32

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.315

Gnomad AMR AF: 0.232

Gnomad ASJ AF: 0.256

Gnomad EAS AF: 0.154

Gnomad SAS AF: 0.213

Gnomad FIN AF: 0.224

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.297

Gnomad OTH AF: 0.233

GnomAD4 exome AF: 0.219 AC: 7 AN: 32 Hom.: 0 Cov.: 0 AF XY: 0.182 AC XY: 4 AN XY: 22

African (AFR) AF: 0.500 AC: 1 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.273 AC: 6 AN: 22

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.230 AC: 34917 AN: 152124 Hom.: 4433 Cov.: 32 AF XY: 0.225 AC XY: 16758 AN XY: 74358

African (AFR) AF: 0.126 AC: 5246 AN: 41502

American (AMR) AF: 0.232 AC: 3543 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.256 AC: 888 AN: 3466

East Asian (EAS) AF: 0.154 AC: 798 AN: 5178

South Asian (SAS) AF: 0.213 AC: 1027 AN: 4812

European-Finnish (FIN) AF: 0.224 AC: 2374 AN: 10580

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.297 AC: 20195 AN: 67984

Other (OTH) AF: 0.232 AC: 490 AN: 2110

Alfa AF: 0.265 Hom.: 7277

Bravo AF: 0.223

Asia WGS AF: 0.185 AC: 644 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.13
DANN	Benign	0.47
PhyloP100		-2.9
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7988959; hg19: chr13-99104004;