Variant 19-10554197-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PM1PM2BP4_Strong

The ENST00000312962.12(KRI1):c.1866C>G(p.Ser622Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000595 in 1,613,996 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00062 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00059 ( 1 hom. )

Consequence

KRI1
ENST00000312962.12 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0500

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]

KRI1 links:

KRI1 (HGNC:):

KRI1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM1

In a modified_residue Phosphoserine (size 0) in uniprot entity KRI1_HUMAN

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.01869592).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRI1	NM_023008.5 linkuse as main transcript	c.1866C>G	p.Ser622Arg	missense_variant	19/19	ENST00000312962.12	NP_075384.4	Q8N9T8A0A494C108
KRI1	XM_047439232.1 linkuse as main transcript	c.1872C>G	p.Ser624Arg	missense_variant	18/18		XP_047295188.1
KRI1	XM_011528190.3 linkuse as main transcript	c.1530C>G	p.Ser510Arg	missense_variant	18/18		XP_011526492.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRI1	ENST00000312962.12 linkuse as main transcript	c.1866C>G	p.Ser622Arg	missense_variant	19/19	1	NM_023008.5	ENSP00000320917.9		Q8N9T8

Frequencies

GnomAD3 genomes

AF:

0.000618

AC:

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000705

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000393

AC:

AN:

246624

Hom.:

AF XY:

0.000447

AC XY:

AN XY:

134292

show subpopulations

Gnomad AFR exome

AF:

0.00106

Gnomad AMR exome

AF:

0.000202

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000229

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000589

Gnomad OTH exome

AF:

0.000330

GnomAD4 exome

AF:

0.000593

AC:

867

AN:

1461718

Hom.:

Cov.:

AF XY:

0.000580

AC XY:

422

AN XY:

727164

show subpopulations

Gnomad4 AFR exome

AF:

0.000866

Gnomad4 AMR exome

AF:

0.000201

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000278

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.000692

Gnomad4 OTH exome

AF:

0.000580

GnomAD4 genome

AF:

0.000617

AC:

AN:

152278

Hom.:

Cov.:

AF XY:

0.000564

AC XY:

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.000962

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000706

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000663

Hom.:

Bravo

AF:

0.000657

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00114

AC:

ESP6500EA

AF:

0.00105

AC:

ExAC

AF:

0.000429

AC:

EpiCase

AF:

0.000654

EpiControl

AF:

0.000296

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 submitter

clinical testing

Ambry Genetics

Jul 20, 2021

The c.1884C>G (p.S628R) alteration is located in exon 19 (coding exon 19) of the KRI1 gene. This alteration results from a C to G substitution at nucleotide position 1884, causing the serine (S) at amino acid position 628 to be replaced by an arginine (R). 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

0.11

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.75

CADD

Benign

2.4

DANN

Benign

0.93

Eigen

Benign

-0.96

Eigen_PC

Benign

-0.93

FATHMM_MKL

Benign

0.23

LIST_S2

Benign

0.33

M_CAP

Benign

0.0064

MetaRNN

Benign

0.019

MetaSVM

Benign

-0.99

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.28

REVEL

Benign

0.033

Sift

Benign

0.16

Sift4G

Benign

0.43

Vest4

0.18

MVP

0.14

MPC

0.21

ClinPred

0.00095

GERP RS

3.2

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over