5-176347748-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_020444.5(KIAA1191):​c.770G>T​(p.Arg257Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000114 in 1,610,108 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R257C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

KIAA1191
NM_020444.5 missense

Scores

6
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.45
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KIAA1191NM_020444.5 linkc.770G>T p.Arg257Leu missense_variant Exon 9 of 9 ENST00000298569.9 NP_065177.2 Q96A73-1A0A024R7Q7

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KIAA1191ENST00000298569.9 linkc.770G>T p.Arg257Leu missense_variant Exon 9 of 9 1 NM_020444.5 ENSP00000298569.4 Q96A73-1

Frequencies

GnomAD3 genomes
AF:
0.0000592
AC:
9
AN:
152096
Hom.:
0
Cov.:
32
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:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000132
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000404
AC:
10
AN:
247238
Hom.:
0
AF XY:
0.0000374
AC XY:
5
AN XY:
133556
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000892
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000119
AC:
174
AN:
1457894
Hom.:
0
Cov.:
31
AF XY:
0.000109
AC XY:
79
AN XY:
725012
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:
0.000149
Gnomad4 OTH exome
AF:
0.000149
GnomAD4 genome
AF:
0.0000591
AC:
9
AN:
152214
Hom.:
0
Cov.:
32
AF XY:
0.0000538
AC XY:
4
AN XY:
74404
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:
0.000132
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000116
Hom.:
0
Bravo
AF:
0.0000718
ExAC
AF:
0.0000412
AC:
5

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 14, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.770G>T (p.R257L) alteration is located in exon 9 (coding exon 7) of the KIAA1191 gene. This alteration results from a G to T substitution at nucleotide position 770, causing the arginine (R) at amino acid position 257 to be replaced by a leucine (L). 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
0.24
BayesDel_addAF
Benign
-0.085
T
BayesDel_noAF
Benign
-0.16
CADD
Benign
18
DANN
Uncertain
1.0
DEOGEN2
Benign
0.19
T;.;.;.;T
Eigen
Benign
-0.043
Eigen_PC
Benign
-0.14
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Benign
0.84
.;.;T;T;T
M_CAP
Benign
0.012
T
MetaRNN
Uncertain
0.52
D;D;D;D;D
MetaSVM
Benign
-0.77
T
MutationAssessor
Uncertain
2.6
M;.;.;.;M
PrimateAI
Benign
0.31
T
PROVEAN
Uncertain
-3.8
D;D;.;.;D
REVEL
Benign
0.14
Sift
Uncertain
0.016
D;D;.;.;D
Sift4G
Benign
0.079
T;T;T;T;T
Polyphen
0.89
P;.;.;.;P
Vest4
0.54
MVP
0.50
MPC
0.49
ClinPred
0.64
D
GERP RS
3.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.41
gMVP
0.12

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.

Other links and lift over

dbSNP: rs202202440; hg19: chr5-175774751; API