chr7-43624552-C-T

Position:

• chr7-43624552-C-T

Variant summary

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

The NM_004760.3(STK17A):​c.955C>T​(p.Pro319Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: STK17A NM_004760.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.35

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]

COA1 (HGNC:21868): (cytochrome c oxidase assembly factor 1) Involved in mitochondrial cytochrome c oxidase assembly and mitochondrial respiratory chain complex I assembly. Located in cytosol and mitochondrion. Is integral component of mitochondrial inner membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STK17A	NM_004760.3	c.955C>T	p.Pro319Ser	missense_variant	7/7	ENST00000319357.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STK17A	ENST00000319357.6	c.955C>T	p.Pro319Ser	missense_variant	7/7	1	NM_004760.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

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

May 23, 2023

The c.955C>T (p.P319S) alteration is located in exon 7 (coding exon 7) of the STK17A gene. This alteration results from a C to T substitution at nucleotide position 955, causing the proline (P) at amino acid position 319 to be replaced by a serine (S). 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	0.10
BayesDel_addAF	Benign	-0.069	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.089	T
Eigen	Uncertain	0.23
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.94	D
M_CAP	Benign	0.0084	T
MetaRNN	Uncertain	0.52	D
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.4	M
MutationTaster	Benign	1.0	D
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.28
Sift	Benign	0.28	T
Sift4G	Benign	0.17	T
Polyphen		0.92	P
Vest4		0.21
MutPred		0.73		Loss of methylation at K317 (P = 0.065);
MVP		0.74
MPC		0.39
ClinPred		0.97	D
GERP RS		4.9
Varity_R		0.20
gMVP		0.42

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: rs976300914; hg19: chr7-43664151;