Genetic Variant ENST00000375333:c.-165T>G (chr6-31972162-T-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000375333.4(WHR1):c.166T>G(p.Trp56Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00021 in 1,612,350 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00022 ( 1 hom. )

Consequence

WHR1
ENST00000375333.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.74

Publications

0 publications found

Variant links:

Genes affected

WHR1 (HGNC:11398): (serine/threonine kinase 19) This gene encodes a serine/threonine kinase which localizes predominantly to the nucleus. Its specific function is unknown; it is possible that phosphorylation of this protein is involved in transcriptional regulation. This gene localizes to the major histocompatibility complex (MHC) class III region on chromosome 6 and expresses two transcript variants. [provided by RefSeq, Jul 2008]

WHR1 links:

DXO (HGNC:2992): (decapping exoribonuclease) This gene localizes to the major histocompatibility complex (MHC) class III region on chromosome 6. The function of its protein product is unknown, but its ubiquitous expression and conservation in both simple and complex eukaryotes suggests that this may be a housekeeping gene. [provided by RefSeq, Jul 2008]

DXO links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.04962516).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000375333.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
WHR1	NM_032454.1		c.166T>G	p.Trp56Gly	missense	Exon 1 of 8	NP_115830.1	P49842-1
WHR1	NR_026717.1		n.394T>G		non_coding_transcript_exon	Exon 2 of 8
DXO	NM_005510.4	MANE Select	c.-240A>C		upstream_gene	N/A	NP_005501.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
WHR1	ENST00000492583.6	TSL:1	c.-250T>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 7	ENSP00000519789.1	P49842-3
WHR1	ENST00000466132.6	TSL:1	c.-250T>G		5_prime_UTR_premature_start_codon_gain	Exon 2 of 8	ENSP00000519788.1	P49842-4
WHR1	ENST00000375333.4	TSL:1	c.166T>G	p.Trp56Gly	missense	Exon 1 of 8	ENSP00000364482.4	P49842-1

Frequencies

GnomAD3 genomes

AF:

0.0000920

AC:

AN:

152096

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.000118

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.0000855

AC:

AN:

245566

AF XY:

0.0000821

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000173

Gnomad OTH exome

AF:

0.000332

GnomAD4 exome

AF:

0.000223

AC:

325

AN:

1460254

Hom.:

Cov.:

AF XY:

0.000180

AC XY:

131

AN XY:

726354

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33470

American (AMR)

AF:

0.0000224

AC:

AN:

44682

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26092

East Asian (EAS)

AF:

0.00

AC:

AN:

39684

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86202

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52456

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.000283

AC:

315

AN:

1111546

Other (OTH)

AF:

0.000133

AC:

AN:

60358

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

104

130

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000920

AC:

AN:

152096

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74304

show subpopulations

African (AFR)

AF:

0.0000724

AC:

AN:

41426

American (AMR)

AF:

0.000131

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10596

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000118

AC:

AN:

67988

Other (OTH)

AF:

0.000478

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000565

Hom.:

Bravo

AF:

0.000140

ExAC

AF:

0.0000248

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.053

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.36

CADD

Benign

1.4

(source)

DANN

Benign

0.52

DEOGEN2

Benign

0.0052

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.0021

LIST_S2

Benign

0.28

M_CAP

Benign

0.010

MetaRNN

Benign

0.050

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.55

PhyloP100

-1.7

PrimateAI

Uncertain

0.58

PROVEAN

Pathogenic

-12

REVEL

Benign

0.037

Sift

Benign

0.12

Sift4G

Benign

0.26

Polyphen

0.0

Vest4

0.070

MVP

0.12

MPC

0.94

ClinPred

0.077

GERP RS

-3.1

PromoterAI

-0.055

Neutral

(source)

Varity_R

0.076

gMVP

0.037

Mutation Taster

=99/1

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over