dbSNP rs150587796: KIAA1586:p.Ser39Leu (chr6-57050784-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_001286275.2(KIAA1586):c.-86C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000732 in 1,611,990 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000063 ( 0 hom. )

Consequence

KIAA1586
NM_001286275.2 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.65

Publications

0 publications found

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:

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=0.0123490095).

BP6

Variant 6-57050784-C-T is Benign according to our data. Variant chr6-57050784-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2363821.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001286275.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KIAA1586	NM_020931.4	MANE Select	c.116C>T	p.Ser39Leu	missense	Exon 3 of 4	NP_065982.1	Q9HCI6-1
KIAA1586	NM_001286275.2		c.-86C>T		5_prime_UTR_premature_start_codon_gain	Exon 3 of 4	NP_001273204.1
KIAA1586	NM_001286276.2		c.-86C>T		5_prime_UTR_premature_start_codon_gain	Exon 3 of 4	NP_001273205.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KIAA1586	ENST00000370733.5	TSL:1 MANE Select	c.116C>T	p.Ser39Leu	missense	Exon 3 of 4	ENSP00000359768.4	Q9HCI6-1
KIAA1586	ENST00000928058.1		c.209C>T	p.Ser70Leu	missense	Exon 4 of 5	ENSP00000598117.1
KIAA1586	ENST00000928059.1		c.128C>T	p.Ser43Leu	missense	Exon 3 of 4	ENSP00000598118.1

Frequencies

GnomAD3 genomes

AF:

0.000171

AC:

AN:

152078

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00141

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000116

AC:

AN:

250978

AF XY:

0.0000737

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000381

Gnomad FIN exome

AF:

0.000554

Gnomad NFE exome

AF:

0.0000793

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000630

AC:

AN:

1459794

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

726378

show subpopulations

African (AFR)

AF:

0.0000300

AC:

AN:

33384

American (AMR)

AF:

0.00

AC:

AN:

44654

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26112

East Asian (EAS)

AF:

0.000252

AC:

AN:

39670

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86152

European-Finnish (FIN)

AF:

0.000318

AC:

AN:

53398

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0000522

AC:

AN:

1110358

Other (OTH)

AF:

0.0000829

AC:

AN:

60300

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

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:

0.000171

AC:

AN:

152196

Hom.:

Cov.:

AF XY:

0.000228

AC XY:

AN XY:

74404

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41528

American (AMR)

AF:

0.00

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000579

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4800

European-Finnish (FIN)

AF:

0.00141

AC:

AN:

10602

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000118

AC:

AN:

68002

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

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:

0.000152

Hom.:

Bravo

AF:

0.0000793

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000988

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.00

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

0.082

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.74

CADD

Benign

2.5

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0018

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0069

LIST_S2

Benign

0.53

M_CAP

Benign

0.0074

MetaRNN

Benign

0.012

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.55

PhyloP100

-2.6

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.070

REVEL

Benign

0.0080

Sift

Uncertain

0.0050

Sift4G

Benign

0.18

Polyphen

0.0070

Vest4

0.13

MVP

0.067

MPC

0.11

ClinPred

0.10

GERP RS

-0.78

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.057

gMVP

0.018

Mutation Taster

=99/1

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