12-75501815-G-T

Position:

chr12-75501815-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_007043.7(KRR1):c.911C>A(p.Ala304Asp) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000687 in 1,601,854 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

KRR1
NM_007043.7 missense, splice_region

Scores

Splicing: ADA: 0.004453

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.97

Variant links:

Genes affected

KRR1 (HGNC:5176): (KRR1 small subunit processome component homolog) Enables RNA binding activity. Predicted to be involved in rRNA processing. Located in chromosome; intercellular bridge; and nuclear lumen. [provided by Alliance of Genome Resources, Apr 2022]

KRR1 links:

GLIPR1 (HGNC:17001): (GLI pathogenesis related 1) This gene encodes a protein with similarity to both the pathogenesis-related protein (PR) superfamily and the cysteine-rich secretory protein (CRISP) family. Increased expression of this gene is associated with myelomocytic differentiation in macrophage and decreased expression of this gene through gene methylation is associated with prostate cancer. The protein has proapoptotic activities in prostate and bladder cancer cells. This gene is a member of a cluster on chromosome 12 containing two other similar genes. Alternatively spliced variants which encode different protein isoforms have been described; however, not all variants have been fully characterized. [provided by RefSeq, Jul 2008]

GLIPR1 links:

KRR1 (HGNC:):

KRR1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.24694702).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRR1	NM_007043.7 linkuse as main transcript	c.911C>A	p.Ala304Asp	missense_variant, splice_region_variant	9/10	ENST00000229214.9	NP_008974.5	Q13601-1
GLIPR1	NM_006851.3 linkuse as main transcript	c.*2837G>T		3_prime_UTR_variant	6/6	ENST00000266659.8	NP_006842.2	P48060-1
KRR1	XM_047428133.1 linkuse as main transcript	c.617C>A	p.Ala206Asp	missense_variant, splice_region_variant	9/10		XP_047284089.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
KRR1	ENST00000229214.9 linkuse as main transcript	c.911C>A	p.Ala304Asp	missense_variant, splice_region_variant	9/10	1	NM_007043.7	ENSP00000229214.4	Q13601-1
KRR1	ENST00000438169.6 linkuse as main transcript	c.740C>A	p.Ala247Asp	missense_variant, splice_region_variant	8/9	1		ENSP00000411740.2	Q13601-2
GLIPR1	ENST00000266659.8 linkuse as main transcript	c.*2837G>T		3_prime_UTR_variant	6/6	1	NM_006851.3	ENSP00000266659.3	P48060-1
KRR1	ENST00000551070.5 linkuse as main transcript	n.459C>A		splice_region_variant, non_coding_transcript_exon_variant	3/4	2

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151470

Hom.:

Cov.:

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:

0.0000295

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000243

AC:

AN:

246820

Hom.:

AF XY:

0.0000374

AC XY:

AN XY:

133652

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:

0.0000538

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000621

AC:

AN:

1450384

Hom.:

Cov.:

AF XY:

0.00000970

AC XY:

AN XY:

721782

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:

0.00000815

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151470

Hom.:

Cov.:

AF XY:

0.0000271

AC XY:

AN XY:

73922

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:

0.0000295

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000494

AC:

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

Jan 11, 2023

The c.911C>A (p.A304D) alteration is located in exon 9 (coding exon 9) of the KRR1 gene. This alteration results from a C to A substitution at nucleotide position 911, causing the alanine (A) at amino acid position 304 to be replaced by an aspartic acid (D). 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

0.27

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.13

T;.

Eigen

Benign

0.16

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.93

D;D

M_CAP

Benign

0.027

MetaRNN

Benign

0.25

T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.6

L;.

PrimateAI

Uncertain

0.59

PROVEAN

Benign

0.090

N;N

REVEL

Benign

0.080

Sift

Benign

0.30

T;T

Sift4G

Benign

0.37

T;T

Polyphen

0.0020

B;.

Vest4

0.41

MVP

0.77

MPC

0.13

ClinPred

0.42

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.20

gMVP

0.33

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0045

dbscSNV1_RF

Benign

0.090

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