Genetic Variant NM_004760.3:c.797A>G (chr7-43623765-A-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_004760.3(STK17A):c.797A>G(p.Asn266Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000653 in 1,608,040 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N266K) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000069 ( 1 hom. )

Consequence

STK17A
NM_004760.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.91

Publications

0 publications found

Variant links:

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]

STK17A links:

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]

COA1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.053365767).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004760.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
STK17A	NM_004760.3	MANE Select	c.797A>G	p.Asn266Ser	missense	Exon 6 of 7	NP_004751.2	Q9UEE5
COA1	NR_135580.2		n.1407+7419T>C		intron	N/A
COA1	NR_135581.2		n.809-14124T>C		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
STK17A	ENST00000319357.6	TSL:1 MANE Select	c.797A>G	p.Asn266Ser	missense	Exon 6 of 7	ENSP00000319192.5	Q9UEE5
STK17A	ENST00000950254.1		c.713A>G	p.Asn238Ser	missense	Exon 5 of 6	ENSP00000620313.1
STK17A	ENST00000869874.1		c.695A>G	p.Asn232Ser	missense	Exon 5 of 6	ENSP00000539933.1

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000106

AC:

AN:

246308

AF XY:

0.000128

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000907

Gnomad ASJ exome

AF:

0.00120

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000267

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000687

AC:

100

AN:

1455716

Hom.:

Cov.:

AF XY:

0.0000788

AC XY:

AN XY:

723794

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33374

American (AMR)

AF:

0.0000688

AC:

AN:

43628

Ashkenazi Jewish (ASJ)

AF:

0.000538

AC:

AN:

26044

East Asian (EAS)

AF:

0.00

AC:

AN:

39414

South Asian (SAS)

AF:

0.000297

AC:

AN:

84300

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53004

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5746

European-Non Finnish (NFE)

AF:

0.0000477

AC:

AN:

1110010

Other (OTH)

AF:

0.0000831

AC:

AN:

60196

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000328

AC:

AN:

152324

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74490

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41588

American (AMR)

AF:

0.00

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.000207

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68010

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000770

Hom.:

Bravo

AF:

0.0000416

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.0000989

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3474

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0045

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.094

FATHMM_MKL

Uncertain

0.96

M_CAP

Benign

0.013

MetaRNN

Benign

0.053

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.56

PhyloP100

6.9

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.38

REVEL

Benign

0.17

Sift

Uncertain

0.015

Sift4G

Uncertain

0.048

Polyphen

0.0040

Vest4

0.070

MVP

0.76

MPC

0.21

ClinPred

0.076

GERP RS

5.0

Varity_R

0.047

gMVP

0.18

Mutation Taster

=90/10

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over