Variant 6-57053053-T-C 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.554T>C(p.Ile185Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000212 in 1,461,328 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: 32)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

KIAA1586
NM_020931.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.369

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:

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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=0.044385493).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIAA1586	NM_020931.4 linkuse as main transcript	c.554T>C	p.Ile185Thr	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.554T>C	p.Ile185Thr	missense_variant	4/4	1	NM_020931.4	ENSP00000359768.4	Q9HCI6-1
KIAA1586	ENST00000545356.5 linkuse as main transcript	c.473T>C	p.Ile158Thr	missense_variant	3/3	2		ENSP00000445507.1	F5H2N6
KIAA1586	ENST00000488682.1 linkuse as main transcript	n.*7T>C		downstream_gene_variant		3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000439

AC:

AN:

250540

Hom.:

AF XY:

0.0000591

AC XY:

AN XY:

135466

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000583

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000197

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000265

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000212

AC:

AN:

1461328

Hom.:

Cov.:

AF XY:

0.0000275

AC XY:

AN XY:

726974

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000448

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000174

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000117

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000494

AC:

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

May 01, 2024

The c.554T>C (p.I185T) alteration is located in exon 4 (coding exon 4) of the KIAA1586 gene. This alteration results from a T to C substitution at nucleotide position 554, causing the isoleucine (I) at amino acid position 185 to be replaced by a threonine (T). 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

0.11

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.43

CADD

Benign

7.2

DANN

Benign

0.94

DEOGEN2

Benign

0.0096

T;T

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.46

FATHMM_MKL

Benign

0.30

LIST_S2

Benign

0.70

T;T

M_CAP

Benign

0.0019

MetaRNN

Benign

0.044

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.34

.;N

PrimateAI

Uncertain

0.55

PROVEAN

Benign

0.12

N;N

REVEL

Benign

0.089

Sift

Uncertain

0.018

D;D

Sift4G

Benign

0.089

T;T

Polyphen

0.020

B;B

Vest4

0.33

MutPred

0.50

.;Gain of disorder (P = 0.0398);

MVP

0.13

MPC

0.037

ClinPred

0.013

GERP RS

2.5

Varity_R

0.088

gMVP

0.038

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

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