chr19-10555319-G-A

Variant summary

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

The NM_023008.5(KRI1):​c.1648C>T​(p.Arg550Trp) variant causes a missense change. The variant allele was found at a frequency of 0.0000359 in 1,614,152 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 34)
Exomes 𝑓: 0.000033 ( 0 hom. )

Consequence

KRI1
NM_023008.5 missense

Scores

6
5
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.09
Variant links:
Genes affected
KRI1 (HGNC:25769): (KRI1 homolog) This gene overlaps with the gene for cysteine endopeptidase AUT-like 4 in a head-to-tail orientation. [provided by RefSeq, Jul 2008]

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/exons MANE UniProt
KRI1NM_023008.5 linkuse as main transcriptc.1648C>T p.Arg550Trp missense_variant 17/19 ENST00000312962.12
KRI1XM_047439232.1 linkuse as main transcriptc.1654C>T p.Arg552Trp missense_variant 16/18
KRI1XM_011528190.3 linkuse as main transcriptc.1312C>T p.Arg438Trp missense_variant 16/18

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
KRI1ENST00000312962.12 linkuse as main transcriptc.1648C>T p.Arg550Trp missense_variant 17/191 NM_023008.5 P2

Frequencies

GnomAD3 genomes
AF:
0.0000657
AC:
10
AN:
152210
Hom.:
0
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000103
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000637
AC:
16
AN:
251206
Hom.:
0
AF XY:
0.0000663
AC XY:
9
AN XY:
135816
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000464
Gnomad NFE exome
AF:
0.000106
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.0000328
AC:
48
AN:
1461824
Hom.:
0
Cov.:
38
AF XY:
0.0000344
AC XY:
25
AN XY:
727212
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.0000360
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.0000656
AC:
10
AN:
152328
Hom.:
0
Cov.:
34
AF XY:
0.0000940
AC XY:
7
AN XY:
74486
show subpopulations
Gnomad4 AFR
AF:
0.0000481
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000103
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000725
Hom.:
0
Bravo
AF:
0.0000529
ExAC
AF:
0.0000741
AC:
9
EpiCase
AF:
0.0000545
EpiControl
AF:
0.000178

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 submitterclinical testingAmbry GeneticsSep 16, 2021The c.1666C>T (p.R556W) alteration is located in exon 17 (coding exon 17) of the KRI1 gene. This alteration results from a C to T substitution at nucleotide position 1666, causing the arginine (R) at amino acid position 556 to be replaced by a tryptophan (W). 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
0.21
BayesDel_addAF
Benign
-0.071
T
BayesDel_noAF
Benign
-0.12
CADD
Pathogenic
33
DANN
Pathogenic
1.0
Eigen
Pathogenic
0.71
Eigen_PC
Pathogenic
0.68
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Pathogenic
0.98
D
M_CAP
Benign
0.023
T
MetaRNN
Uncertain
0.66
D
MetaSVM
Benign
-1.1
T
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.67
T
PROVEAN
Pathogenic
-5.1
D
REVEL
Uncertain
0.31
Sift
Uncertain
0.0010
D
Sift4G
Uncertain
0.0070
D
Vest4
0.71
MVP
0.60
MPC
0.64
ClinPred
0.88
D
GERP RS
5.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs200050484; hg19: chr19-10665995; COSMIC: COSV57265517; COSMIC: COSV57265517; API