13-98463584-TAAAAA-TAAAAAAAAAA

Variant names:

• chr13-98463584-T-TAAAAA
• rs56325686
• NM_001032296.4:c.929+102_929+106dupTTTTT

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001032296.4(STK24):​c.929+102_929+106dupTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000331 in 906,582 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.0000033 (0 hom.)
• Consequence: STK24 NM_001032296.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.20
• Publications: 0 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001032296.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STK24	NM_001032296.4	MANE Select	c.929+102_929+106dupTTTTT		intron	N/A	NP_001027467.2
	STK24	NM_003576.5		c.965+102_965+106dupTTTTT		intron	N/A	NP_003567.2
	STK24	NM_001286649.2		c.872+102_872+106dupTTTTT		intron	N/A	NP_001273578.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STK24	ENST00000539966.6	TSL:1 MANE Select	c.929+106_929+107insTTTTT		intron	N/A	ENSP00000442539.2
	STK24	ENST00000376547.7	TSL:1	c.965+106_965+107insTTTTT		intron	N/A	ENSP00000365730.3
	STK24	ENST00000444574.1	TSL:1	c.680+106_680+107insTTTTT		intron	N/A	ENSP00000402764.1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.00000331 AC: 3 AN: 906582 Hom.: 0 AF XY: 0.00000224 AC XY: 1 AN XY: 447176

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 21338

American (AMR) AF: 0.00 AC: 0 AN: 15654

Ashkenazi Jewish (ASJ) AF: 0.0000675 AC: 1 AN: 14816

East Asian (EAS) AF: 0.00 AC: 0 AN: 28366

South Asian (SAS) AF: 0.00 AC: 0 AN: 47894

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 25700

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4090

European-Non Finnish (NFE) AF: 0.00000282 AC: 2 AN: 709302

Other (OTH) AF: 0.00 AC: 0 AN: 39422

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.2

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs56325686; hg19: chr13-99115838;