Variant 6-57052711-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_020931.4(KIAA1586):c.212G>A(p.Arg71Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000183 in 1,566,574 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: 𝑓 0.00016 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00018 ( 0 hom. )

Consequence

KIAA1586
NM_020931.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.119

Variant links:

Genes affected

KIAA1586 (HGNC:21360): (KIAA1586) Enables SUMO ligase activity. Involved in protein sumoylation. [provided by Alliance of Genome Resources, Apr 2022]

KIAA1586 links:

KIAA1586 (HGNC:):

KIAA1586 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.027260125).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIAA1586	NM_020931.4 linkuse as main transcript	c.212G>A	p.Arg71Gln	missense_variant	4/4	ENST00000370733.5	NP_065982.1	Q9HCI6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
KIAA1586	ENST00000370733.5 linkuse as main transcript	c.212G>A	p.Arg71Gln	missense_variant	4/4	1	NM_020931.4	ENSP00000359768.4	Q9HCI6-1
KIAA1586	ENST00000545356.5 linkuse as main transcript	c.131G>A	p.Arg44Gln	missense_variant	3/3	2		ENSP00000445507.1	F5H2N6
KIAA1586	ENST00000488682.1 linkuse as main transcript	n.366G>A		non_coding_transcript_exon_variant	4/4	3

Frequencies

GnomAD3 genomes

AF:

0.000164

AC:

AN:

152014

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000484

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000338

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000152

AC:

AN:

224272

Hom.:

AF XY:

0.000205

AC XY:

AN XY:

122122

show subpopulations

Gnomad AFR exome

AF:

0.0000655

Gnomad AMR exome

AF:

0.0000383

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000390

Gnomad FIN exome

AF:

0.0000968

Gnomad NFE exome

AF:

0.000273

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000185

AC:

261

AN:

1414560

Hom.:

Cov.:

AF XY:

0.000183

AC XY:

128

AN XY:

700626

show subpopulations

Gnomad4 AFR exome

AF:

0.0000639

Gnomad4 AMR exome

AF:

0.0000285

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000898

Gnomad4 FIN exome

AF:

0.000115

Gnomad4 NFE exome

AF:

0.000210

Gnomad4 OTH exome

AF:

0.000257

GnomAD4 genome

AF:

0.000164

AC:

AN:

152014

Hom.:

Cov.:

AF XY:

0.000162

AC XY:

AN XY:

74254

show subpopulations

Gnomad4 AFR

AF:

0.0000484

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000338

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000283

Hom.:

Bravo

AF:

0.000162

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000157

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3476

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 03, 2022

The c.212G>A (p.R71Q) alteration is located in exon 4 (coding exon 4) of the KIAA1586 gene. This alteration results from a G to A substitution at nucleotide position 212, causing the arginine (R) at amino acid position 71 to be replaced by a glutamine (Q). 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

-0.37

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.011

T;T

Eigen

Benign

-0.77

Eigen_PC

Benign

-0.71

FATHMM_MKL

Benign

0.091

LIST_S2

Benign

0.81

T;T

M_CAP

Benign

0.0029

MetaRNN

Benign

0.027

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.55

.;N

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.63

N;N

REVEL

Benign

0.061

Sift

Pathogenic

0.0

D;D

Sift4G

Benign

0.066

T;T

Polyphen

0.0060

B;B

Vest4

0.34

MVP

0.092

MPC

0.13

ClinPred

0.092

GERP RS

2.1

Varity_R

0.19

gMVP

0.059

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over