Variant 22-35264882-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001003681.3(HMGXB4):c.494G>T(p.Gly165Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.613 in 1,613,482 control chromosomes in the GnomAD database, including 313,208 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.50 ( 22276 hom., cov: 31)

Exomes 𝑓: 0.62 ( 290932 hom. )

Consequence

HMGXB4
NM_001003681.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.34

Variant links:

Genes affected

HMGXB4 (HGNC:5003): (HMG-box containing 4) High mobility group (HMG) proteins are nonhistone chromosomal proteins. See HMG2 (MIM 163906) for additional information on HMG proteins.[supplied by OMIM, Nov 2010]

HMGXB4 links:

HMGXB4 (HGNC:):

HMGXB4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=6.2052422E-6).

BP6

Variant 22-35264882-G-T is Benign according to our data. Variant chr22-35264882-G-T is described in ClinVar as [Benign]. Clinvar id is 1235870.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.646 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HMGXB4	NM_001003681.3 linkuse as main transcript	c.494G>T	p.Gly165Val	missense_variant	5/11	ENST00000216106.6	NP_001003681.1	Q9UGU5Q7Z641

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HMGXB4	ENST00000216106.6 linkuse as main transcript	c.494G>T	p.Gly165Val	missense_variant	5/11	5	NM_001003681.3	ENSP00000216106.5		Q9UGU5

Frequencies

GnomAD3 genomes

AF:

0.498

AC:

75542

AN:

151826

Hom.:

22292

Cov.:

show subpopulations

Gnomad AFR

AF:

0.158

Gnomad AMI

AF:

0.673

Gnomad AMR

AF:

0.557

Gnomad ASJ

AF:

0.689

Gnomad EAS

AF:

0.539

Gnomad SAS

AF:

0.569

Gnomad FIN

AF:

0.606

Gnomad MID

AF:

0.604

Gnomad NFE

AF:

0.651

Gnomad OTH

AF:

0.570

GnomAD3 exomes

AF:

0.585

AC:

146960

AN:

251232

Hom.:

44852

AF XY:

0.594

AC XY:

80730

AN XY:

135816

show subpopulations

Gnomad AFR exome

AF:

0.147

Gnomad AMR exome

AF:

0.564

Gnomad ASJ exome

AF:

0.686

Gnomad EAS exome

AF:

0.538

Gnomad SAS exome

AF:

0.569

Gnomad FIN exome

AF:

0.606

Gnomad NFE exome

AF:

0.651

Gnomad OTH exome

AF:

0.620

GnomAD4 exome

AF:

0.625

AC:

913117

AN:

1461538

Hom.:

290932

Cov.:

AF XY:

0.625

AC XY:

454348

AN XY:

727070

show subpopulations

Gnomad4 AFR exome

AF:

0.136

Gnomad4 AMR exome

AF:

0.564

Gnomad4 ASJ exome

AF:

0.686

Gnomad4 EAS exome

AF:

0.525

Gnomad4 SAS exome

AF:

0.570

Gnomad4 FIN exome

AF:

0.598

Gnomad4 NFE exome

AF:

0.651

Gnomad4 OTH exome

AF:

0.609

GnomAD4 genome

AF:

0.497

AC:

75518

AN:

151944

Hom.:

22276

Cov.:

AF XY:

0.497

AC XY:

36882

AN XY:

74244

show subpopulations

Gnomad4 AFR

AF:

0.157

Gnomad4 AMR

AF:

0.557

Gnomad4 ASJ

AF:

0.689

Gnomad4 EAS

AF:

0.539

Gnomad4 SAS

AF:

0.568

Gnomad4 FIN

AF:

0.606

Gnomad4 NFE

AF:

0.651

Gnomad4 OTH

AF:

0.569

Alfa

AF:

0.625

Hom.:

75096

Bravo

AF:

0.482

TwinsUK

AF:

0.654

AC:

2425

ALSPAC

AF:

0.655

AC:

2523

ESP6500AA

AF:

0.165

AC:

728

ESP6500EA

AF:

0.655

AC:

5637

ExAC

AF:

0.578

AC:

70120

Asia WGS

AF:

0.532

AC:

1852

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 19, 2019	This variant is associated with the following publications: (PMID: 30389748) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.059

T;.;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.48

LIST_S2

Benign

0.53

T;T;T

MetaRNN

Benign

0.0000062

T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.55

.;.;N

PrimateAI

Benign

0.24

PROVEAN

Uncertain

-2.5

D;D;N

REVEL

Benign

0.12

Sift

Uncertain

0.018

D;D;D

Sift4G

Benign

0.061

T;T;D

Polyphen

0.012

.;.;B

Vest4

0.18

MPC

0.18

ClinPred

0.018

GERP RS

1.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.058

gMVP

0.11

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