chr7-43583271-G-T

Position:

• chr7-43583271-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004760.3(STK17A):​c.28G>T​(p.Gly10Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000151 in 1,393,202 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000015 (0 hom.)
• Consequence: STK17A NM_004760.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0280

Genes affected

STK17A (HGNC:11395): (serine/threonine kinase 17a) This gene is a member of the DAP kinase-related apoptosis-inducing protein kinase family and encodes an autophosphorylated nuclear protein with a protein kinase domain. The protein has apoptosis-inducing activity. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22707662).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STK17A	NM_004760.3	c.28G>T	p.Gly10Cys	missense_variant	1/7	ENST00000319357.6	NP_004751.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STK17A	ENST00000319357.6	c.28G>T	p.Gly10Cys	missense_variant	1/7	1	NM_004760.3	ENSP00000319192	P1
STK17A	ENST00000648544.1	c.28G>T	p.Gly10Cys	missense_variant, NMD_transcript_variant	1/9			ENSP00000497301
STK17A	ENST00000462448.1	n.204+310G>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.0000151 AC: 21 AN: 1393202 Hom.: 0 Cov.: 33 AF XY: 0.0000144 AC XY: 10 AN XY: 693154

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000668

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 03, 2024

The c.28G>T (p.G10C) alteration is located in exon 1 (coding exon 1) of the STK17A gene. This alteration results from a G to T substitution at nucleotide position 28, causing the glycine (G) at amino acid position 10 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	17
DANN	Benign	0.65
DEOGEN2	Benign	0.016	T
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.041	N
M_CAP	Pathogenic	0.32	D
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	1.6	L
MutationTaster	Benign	1.0	N
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	0.16	N
REVEL	Benign	0.11
Sift	Benign	0.16	T
Sift4G	Uncertain	0.010	D
Polyphen		1.0	D
Vest4		0.14
MutPred		0.38		Loss of relative solvent accessibility (P = 0.0186);
MVP		0.76
MPC		0.28
ClinPred		0.63	D
GERP RS		1.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.6
Varity_R		0.12
gMVP		0.60

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: rs904358428; hg19: chr7-43622870;