Variant chr6-57046775-A-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_020931.4(KIAA1586):c.20A>T(p.Glu7Val) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

KIAA1586
NM_020931.4 missense, splice_region

Scores

Splicing: ADA: 0.9983

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.19

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 Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIAA1586	NM_020931.4 linkuse as main transcript	c.20A>T	p.Glu7Val	missense_variant, splice_region_variant	1/4	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.20A>T	p.Glu7Val	missense_variant, splice_region_variant	1/4	1	NM_020931.4	ENSP00000359768.4	Q9HCI6-1
KIAA1586	ENST00000545356.5 linkuse as main transcript	c.20A>T	p.Glu7Val	missense_variant, splice_region_variant	1/3	2		ENSP00000445507.1	F5H2N6
KIAA1586	ENST00000488682.1 linkuse as main transcript	n.29A>T		non_coding_transcript_exon_variant	1/4	3

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

151834

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000616

AC:

AN:

1460052

Hom.:

Cov.:

AF XY:

0.00000551

AC XY:

AN XY:

726282

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000720

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000132

AC:

AN:

151834

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74136

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

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

Nov 15, 2024

The c.20A>T (p.E7V) alteration is located in exon 1 (coding exon 1) of the KIAA1586 gene. This alteration results from a A to T substitution at nucleotide position 20, causing the glutamic acid (E) at amino acid position 7 to be replaced by a valine (V). 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

0.19

BayesDel_addAF

Benign

-0.051

BayesDel_noAF

Benign

-0.31

CADD

Pathogenic

DANN

Benign

0.97

DEOGEN2

Benign

0.023

T;T

Eigen

Benign

-0.47

Eigen_PC

Benign

-0.55

FATHMM_MKL

Benign

0.49

LIST_S2

Uncertain

0.90

D;D

M_CAP

Benign

0.046

MetaRNN

Benign

0.17

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

.;N

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-1.3

N;N

REVEL

Benign

0.084

Sift

Pathogenic

0.0

D;D

Sift4G

Uncertain

0.010

D;D

Polyphen

0.46

P;P

Vest4

0.19

MutPred

0.34

Gain of sheet (P = 0.0221);Gain of sheet (P = 0.0221);

MVP

0.42

MPC

0.22

ClinPred

0.54

GERP RS

0.89

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.18

gMVP

0.12

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.86

SpliceAI score (max)

0.35

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.31

Position offset: -6

DS_DL_spliceai

0.35

Position offset: 1

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