Genetic Variant ATPSCKMT:p.Arg86Gln (chr5-10239116-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_199133.4(ATPSCKMT):c.257G>A(p.Arg86Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00027 in 1,614,076 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00028 ( 0 hom. )

Consequence

ATPSCKMT
NM_199133.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.355

Publications

2 publications found

Variant links:

Genes affected

ATPSCKMT (HGNC:27029): (ATP synthase c subunit lysine N-methyltransferase) Enables protein-lysine N-methyltransferase activity. Involved in peptidyl-lysine trimethylation; positive regulation of sensory perception of pain; and regulation of proton transport. Located in mitochondrial crista. [provided by Alliance of Genome Resources, Apr 2022]

ATPSCKMT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.033463597).

BP6

Variant 5-10239116-C-T is Benign according to our data. Variant chr5-10239116-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3132095.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_199133.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ATPSCKMT	NM_199133.4	MANE Select	c.257G>A	p.Arg86Gln	missense	Exon 2 of 5	NP_954584.2	Q6P4H8-1
ATPSCKMT	NM_001258388.2		c.257G>A	p.Arg86Gln	missense	Exon 2 of 4	NP_001245317.1	Q6P4H8-2
ATPSCKMT	NM_001258389.2		c.257G>A	p.Arg86Gln	missense	Exon 2 of 5	NP_001245318.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ATPSCKMT	ENST00000511437.6	TSL:1 MANE Select	c.257G>A	p.Arg86Gln	missense	Exon 2 of 5	ENSP00000422338.1	Q6P4H8-1
ATPSCKMT	ENST00000932928.1		c.257G>A	p.Arg86Gln	missense	Exon 2 of 5	ENSP00000602987.1
ATPSCKMT	ENST00000510047.5	TSL:2	c.257G>A	p.Arg86Gln	missense	Exon 2 of 4	ENSP00000420876.1	Q6P4H8-2

Frequencies

GnomAD3 genomes

AF:

0.000138

AC:

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000265

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000104

AC:

AN:

249556

AF XY:

0.0000960

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000212

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.000283

AC:

414

AN:

1461880

Hom.:

Cov.:

AF XY:

0.000274

AC XY:

199

AN XY:

727242

show subpopulations

African (AFR)

AF:

0.0000597

AC:

AN:

33480

American (AMR)

AF:

0.0000224

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53408

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000362

AC:

402

AN:

1112010

Other (OTH)

AF:

0.000149

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

116

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<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:

0.000138

AC:

AN:

152196

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.0000483

AC:

AN:

41436

American (AMR)

AF:

0.0000655

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5206

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000265

AC:

AN:

68040

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.518

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:

0.000343

Hom.:

Bravo

AF:

0.000151

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000120

AC:

ExAC

AF:

0.0000579

AC:

EpiCase

AF:

0.000327

EpiControl

AF:

0.000296

ClinVar

ClinVar submissions

Significance:Likely benign

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

0.063

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.059

(source)

DANN

Benign

0.69

DEOGEN2

Benign

0.0014

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.1

FATHMM_MKL

Benign

0.018

LIST_S2

Benign

0.54

M_CAP

Benign

0.0070

MetaRNN

Benign

0.033

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.050

PhyloP100

-0.35

PrimateAI

Benign

0.22

PROVEAN

Benign

-0.38

REVEL

Benign

0.084

Sift

Benign

0.68

Sift4G

Benign

0.61

Polyphen

0.022

Vest4

0.082

MVP

0.030

MPC

0.088

ClinPred

0.021

GERP RS

-10

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.013

gMVP

0.37

Mutation Taster

=92/8

polymorphism

(source)

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

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