Genetic Variant KIAA1191:p.Ala289Thr (chr5-176347653-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_020444.5(KIAA1191):c.865G>A(p.Ala289Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000122 in 1,562,786 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000012 ( 1 hom. )

Consequence

KIAA1191
NM_020444.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0410

Publications

0 publications found

Variant links:

Genes affected

KIAA1191 (HGNC:29209): (KIAA1191) Predicted to enable oxidoreductase activity. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

KIAA1191 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=0.018256932).

BP6

Variant 5-176347653-C-T is Benign according to our data. Variant chr5-176347653-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3863697.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020444.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KIAA1191	NM_020444.5	MANE Select	c.865G>A	p.Ala289Thr	missense	Exon 9 of 9	NP_065177.2
KIAA1191	NM_001079685.3		c.865G>A	p.Ala289Thr	missense	Exon 8 of 8	NP_001073153.1	Q96A73-1
KIAA1191	NM_001079684.3		c.808G>A	p.Ala270Thr	missense	Exon 8 of 8	NP_001073152.1	Q96A73-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KIAA1191	ENST00000298569.9	TSL:1 MANE Select	c.865G>A	p.Ala289Thr	missense	Exon 9 of 9	ENSP00000298569.4	Q96A73-1
KIAA1191	ENST00000510164.5	TSL:1	c.865G>A	p.Ala289Thr	missense	Exon 8 of 8	ENSP00000421061.1	Q96A73-1
KIAA1191	ENST00000393725.6	TSL:1	c.808G>A	p.Ala270Thr	missense	Exon 8 of 8	ENSP00000377326.2	Q96A73-2

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152102

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000532

AC:

AN:

206646

AF XY:

0.0000364

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000411

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000121

AC:

AN:

1410684

Hom.:

Cov.:

AF XY:

0.0000100

AC XY:

AN XY:

697514

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31590

American (AMR)

AF:

0.000363

AC:

AN:

35814

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22428

East Asian (EAS)

AF:

0.00

AC:

AN:

39366

South Asian (SAS)

AF:

0.00

AC:

AN:

76310

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51642

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5486

European-Non Finnish (NFE)

AF:

0.00000367

AC:

AN:

1089792

Other (OTH)

AF:

0.00

AC:

AN:

58256

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.0000131

AC:

AN:

152102

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74294

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41426

American (AMR)

AF:

0.000131

AC:

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10602

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68012

Other (OTH)

AF:

0.00

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

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:

0.0000156

Hom.:

Bravo

AF:

0.0000567

ExAC

AF:

0.0000412

AC:

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

0.065

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.69

CADD

Benign

8.1

(source)

DANN

Benign

0.62

DEOGEN2

Benign

0.0065

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.056

LIST_S2

Benign

0.57

M_CAP

Benign

0.0021

MetaRNN

Benign

0.018

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.0

PhyloP100

0.041

PrimateAI

Benign

0.25

PROVEAN

Benign

1.3

REVEL

Benign

0.20

Sift

Benign

1.0

Sift4G

Benign

0.64

Polyphen

0.0

Vest4

0.015

MutPred

0.090

Gain of relative solvent accessibility (P = 0.0215)

MVP

0.14

MPC

0.26

ClinPred

0.023

GERP RS

-4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.016

gMVP

0.085

Mutation Taster

=100/0

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