13-98446064-C-T

Variant names:

• chr13-98446064-C-T
• rs2274053
• NM_001032296.4:c.*7109G>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.*7109G>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 0.802 in 1,464,782 control chromosomes in the GnomAD database, including 477,714 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 0.76 (44488 hom., cov: 35)
  • Exomes 𝑓: 0.81 (433226 hom.)
• Consequence: STK24 NM_001032296.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.175
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.836 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STK24	NM_001032296.4	c.*7109G>A		3_prime_UTR_variant	Exon 11 of 11	ENST00000539966.6	NP_001027467.2
FARP1	NM_005766.4	c.2797-34C>T		intron_variant	Intron 24 of 26	ENST00000319562.11	NP_005757.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STK24	ENST00000539966.6	c.*7109G>A		3_prime_UTR_variant	Exon 11 of 11	1	NM_001032296.4	ENSP00000442539.2
FARP1	ENST00000319562.11	c.2797-34C>T		intron_variant	Intron 24 of 26	1	NM_005766.4	ENSP00000322926.6

Frequencies

GnomAD3 genomes AF: 0.757 AC: 115197 AN: 152108 Hom.: 44463 Cov.: 35

Gnomad AFR AF: 0.655

Gnomad AMI AF: 0.929

Gnomad AMR AF: 0.673

Gnomad ASJ AF: 0.777

Gnomad EAS AF: 0.628

Gnomad SAS AF: 0.588

Gnomad FIN AF: 0.859

Gnomad MID AF: 0.680

Gnomad NFE AF: 0.841

Gnomad OTH AF: 0.752

GnomAD2 exomes AF: 0.745 AC: 183227 AN: 246026 AF XY: 0.747

Gnomad AFR exome AF: 0.651

Gnomad AMR exome AF: 0.582

Gnomad ASJ exome AF: 0.784

Gnomad EAS exome AF: 0.619

Gnomad FIN exome AF: 0.859

Gnomad NFE exome AF: 0.841

Gnomad OTH exome AF: 0.768

GnomAD4 exome AF: 0.808 AC: 1060212 AN: 1312556 Hom.: 433226 Cov.: 18 AF XY: 0.802 AC XY: 529833 AN XY: 660548

African (AFR) AF: 0.646 AC: 19864 AN: 30740

American (AMR) AF: 0.590 AC: 26049 AN: 44114

Ashkenazi Jewish (ASJ) AF: 0.781 AC: 19386 AN: 24832

East Asian (EAS) AF: 0.669 AC: 26099 AN: 38984

South Asian (SAS) AF: 0.605 AC: 49934 AN: 82570

European-Finnish (FIN) AF: 0.855 AC: 45427 AN: 53102

Middle Eastern (MID) AF: 0.703 AC: 3805 AN: 5412

European-Non Finnish (NFE) AF: 0.845 AC: 825713 AN: 977216

Other (OTH) AF: 0.790 AC: 43935 AN: 55586

GnomAD4 genome AF: 0.757 AC: 115268 AN: 152226 Hom.: 44488 Cov.: 35 AF XY: 0.753 AC XY: 56046 AN XY: 74416

African (AFR) AF: 0.656 AC: 27234 AN: 41528

American (AMR) AF: 0.673 AC: 10291 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.777 AC: 2699 AN: 3472

East Asian (EAS) AF: 0.627 AC: 3238 AN: 5164

South Asian (SAS) AF: 0.588 AC: 2838 AN: 4828

European-Finnish (FIN) AF: 0.859 AC: 9115 AN: 10608

Middle Eastern (MID) AF: 0.673 AC: 198 AN: 294

European-Non Finnish (NFE) AF: 0.841 AC: 57224 AN: 68010

Other (OTH) AF: 0.750 AC: 1584 AN: 2112

Alfa AF: 0.797 Hom.: 9097

Bravo AF: 0.737

Asia WGS AF: 0.630 AC: 2192 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.4
DANN	Benign	0.39
PhyloP100		-0.17
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs2274053; hg19: chr13-99098318; COSMIC: COSV60342092; COSMIC: COSV60342092;