chr13-98448220-C-T

Variant names:

• chr13-98448220-C-T
• rs9517310
• NM_001032296.4:c.*4953G>A

Variant summary

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

The NM_001032296.4(STK24):​c.*4953G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 1,607,738 control chromosomes in the GnomAD database, including 64,944 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 (4629 hom., cov: 33)
  • Exomes 𝑓: 0.28 (60315 hom.)
• Consequence: STK24 NM_001032296.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.211
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.303 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STK24	NM_001032296.4	c.*4953G>A		3_prime_UTR_variant	Exon 11 of 11	ENST00000539966.6	NP_001027467.2
FARP1	NM_005766.4	c.3057-16C>T		intron_variant	Intron 26 of 26	ENST00000319562.11	NP_005757.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STK24	ENST00000539966.6	c.*4953G>A		3_prime_UTR_variant	Exon 11 of 11	1	NM_001032296.4	ENSP00000442539.2
FARP1	ENST00000319562.11	c.3057-16C>T		intron_variant	Intron 26 of 26	1	NM_005766.4	ENSP00000322926.6
FARP1	ENST00000595437.5	c.3150-16C>T		intron_variant	Intron 27 of 27	1		ENSP00000471242.1
FARP1	ENST00000627049.2	c.3150-16C>T		intron_variant	Intron 27 of 27	5		ENSP00000486285.1

Frequencies

GnomAD3 genomes AF: 0.234 AC: 35572 AN: 152054 Hom.: 4626 Cov.: 33

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.318

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.258

Gnomad EAS AF: 0.154

Gnomad SAS AF: 0.211

Gnomad FIN AF: 0.236

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.306

Gnomad OTH AF: 0.239

GnomAD2 exomes AF: 0.250 AC: 62752 AN: 251134 AF XY: 0.254

Gnomad AFR exome AF: 0.123

Gnomad AMR exome AF: 0.214

Gnomad ASJ exome AF: 0.263

Gnomad EAS exome AF: 0.159

Gnomad FIN exome AF: 0.247

Gnomad NFE exome AF: 0.299

Gnomad OTH exome AF: 0.248

GnomAD4 exome AF: 0.283 AC: 411764 AN: 1455566 Hom.: 60315 Cov.: 29 AF XY: 0.282 AC XY: 204544 AN XY: 724462

African (AFR) AF: 0.116 AC: 3863 AN: 33346

American (AMR) AF: 0.214 AC: 9547 AN: 44688

Ashkenazi Jewish (ASJ) AF: 0.262 AC: 6838 AN: 26102

East Asian (EAS) AF: 0.144 AC: 5717 AN: 39674

South Asian (SAS) AF: 0.230 AC: 19805 AN: 86110

European-Finnish (FIN) AF: 0.258 AC: 13784 AN: 53412

Middle Eastern (MID) AF: 0.213 AC: 1197 AN: 5612

European-Non Finnish (NFE) AF: 0.303 AC: 335137 AN: 1106480

Other (OTH) AF: 0.264 AC: 15876 AN: 60142

GnomAD4 genome AF: 0.234 AC: 35583 AN: 152172 Hom.: 4629 Cov.: 33 AF XY: 0.230 AC XY: 17108 AN XY: 74394

African (AFR) AF: 0.123 AC: 5087 AN: 41526

American (AMR) AF: 0.236 AC: 3613 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.258 AC: 897 AN: 3472

East Asian (EAS) AF: 0.154 AC: 798 AN: 5176

South Asian (SAS) AF: 0.211 AC: 1021 AN: 4832

European-Finnish (FIN) AF: 0.236 AC: 2499 AN: 10568

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.306 AC: 20807 AN: 67986

Other (OTH) AF: 0.238 AC: 503 AN: 2112

Alfa AF: 0.277 Hom.: 10613

Bravo AF: 0.226

Asia WGS AF: 0.184 AC: 640 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.9
DANN	Benign	0.72
PhyloP100		-0.21
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: rs9517310; hg19: chr13-99100474; COSMIC: COSV60342680; COSMIC: COSV60342680;