Genetic Variant KIAA1191:p.Met263Ile (chr5-176347729-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_020444.5(KIAA1191):c.789G>A(p.Met263Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,457,862 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

KIAA1191
NM_020444.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.54

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:

KIAA1191-AS1 (HGNC:41234):

KIAA1191-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07313472).

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.789G>A	p.Met263Ile	missense	Exon 9 of 9	NP_065177.2
KIAA1191	NM_001079685.3		c.789G>A	p.Met263Ile	missense	Exon 8 of 8	NP_001073153.1	Q96A73-1
KIAA1191	NM_001079684.3		c.732G>A	p.Met244Ile	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.789G>A	p.Met263Ile	missense	Exon 9 of 9	ENSP00000298569.4	Q96A73-1
KIAA1191	ENST00000510164.5	TSL:1	c.789G>A	p.Met263Ile	missense	Exon 8 of 8	ENSP00000421061.1	Q96A73-1
KIAA1191	ENST00000393725.6	TSL:1	c.732G>A	p.Met244Ile	missense	Exon 8 of 8	ENSP00000377326.2	Q96A73-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000809

AC:

AN:

247330

AF XY:

0.00000748

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000595

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:

0.00000206

AC:

AN:

1457862

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725078

show subpopulations

African (AFR)

AF:

0.0000301

AC:

AN:

33270

American (AMR)

AF:

0.0000456

AC:

AN:

43846

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25886

East Asian (EAS)

AF:

0.00

AC:

AN:

39674

South Asian (SAS)

AF:

0.00

AC:

AN:

85588

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53298

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5738

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110376

Other (OTH)

AF:

0.00

AC:

AN:

60186

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

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

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

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

0.25

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.58

CADD

Benign

(source)

DANN

Benign

0.61

DEOGEN2

Benign

0.029

Eigen

Benign

-0.76

Eigen_PC

Benign

-0.68

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.61

M_CAP

Benign

0.0023

MetaRNN

Benign

0.073

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.0

PhyloP100

1.5

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.0

REVEL

Benign

0.044

Sift

Benign

0.45

Sift4G

Benign

0.96

Polyphen

0.0

Vest4

0.083

MutPred

0.16

Gain of helix (P = 0.132)

MVP

0.37

MPC

0.30

ClinPred

0.024

GERP RS

2.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.033

gMVP

0.067

Mutation Taster

=96/4

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over