Variant 3-42941975-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001205272.2(KRBOX1):c.181C>T(p.Pro61Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000117 in 1,535,608 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000051 ( 0 hom. )

Consequence

KRBOX1
NM_001205272.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.28

Variant links:

Genes affected

KRBOX1 (HGNC:38708): (KRAB box domain containing 1) Predicted to be involved in regulation of transcription, DNA-templated. [provided by Alliance of Genome Resources, Apr 2022]

KRBOX1 links:

ENSG00000290317 (HGNC:):

ENSG00000290317 links:

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	Protein	UniProt
KRBOX1	NM_001205272.2 linkuse as main transcript	c.181C>T	p.Pro61Ser	missense_variant	4/5	ENST00000383748.9	NP_001192201.1	C9JBD0-1A0A024R2N1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
KRBOX1	ENST00000383748.9 linkuse as main transcript	c.181C>T	p.Pro61Ser	missense_variant	4/5	1	NM_001205272.2	ENSP00000373254.5	C9JBD0-1
ENSG00000290317	ENST00000426937.5 linkuse as main transcript	c.181C>T	p.Pro61Ser	missense_variant	6/7	3		ENSP00000413859.1
ENSG00000273291	ENST00000446977.2 linkuse as main transcript	c.181C>T	p.Pro61Ser	missense_variant	4/5	4		ENSP00000477043.1	V9GYS6

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000729

AC:

AN:

137116

Hom.:

AF XY:

0.0000134

AC XY:

AN XY:

74526

show subpopulations

Gnomad AFR exome

AF:

0.000155

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000506

AC:

AN:

1383452

Hom.:

Cov.:

AF XY:

0.00000732

AC XY:

AN XY:

682698

show subpopulations

Gnomad4 AFR exome

AF:

0.0000317

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:

0.00000556

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000723

AC:

AN:

152156

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.000193

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:

0.0000441

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000680

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

Mar 08, 2024

The c.181C>T (p.P61S) alteration is located in exon 4 (coding exon 3) of the KRBOX1 gene. This alteration results from a C to T substitution at nucleotide position 181, causing the proline (P) at amino acid position 61 to be replaced by a serine (S). 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

Uncertain

0.42

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.10

.;T;T;T

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.54

T;.;.;T

M_CAP

Benign

0.011

MetaRNN

Uncertain

0.46

T;T;T;T

MetaSVM

Benign

-1.2

MutationAssessor

Benign

1.4

.;L;L;L

PrimateAI

Benign

0.26

PROVEAN

Pathogenic

-8.0

.;D;D;D

REVEL

Benign

0.11

Sift

Uncertain

0.0010

.;D;D;D

Sift4G

Pathogenic

0.0010

D;D;D;D

Polyphen

1.0

.;D;D;D

Vest4

0.15, 0.42, 0.42

MutPred

0.51

Loss of glycosylation at T58 (P = 0.0564);Loss of glycosylation at T58 (P = 0.0564);Loss of glycosylation at T58 (P = 0.0564);Loss of glycosylation at T58 (P = 0.0564);

MVP

0.29

MPC

0.42

ClinPred

1.0

GERP RS

4.4

Varity_R

0.38

gMVP

0.081

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.

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