Variant chr5-150006645-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_014983.3(HMGXB3):c.310C>T(p.Pro104Ser) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000000715 in 1,398,476 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

HMGXB3
NM_014983.3 missense, splice_region

Scores

Splicing: ADA: 0.9998

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.73

Variant links:

Genes affected

HMGXB3 (HGNC:28982): (HMG-box containing 3) This gene is one of the non-canonical high mobility group (HMG) genes. The encoded protein contains an HMG-box domain found in DNA binding proteins such as transcription factors and chromosomal proteins. [provided by RefSeq, Aug 2011]

HMGXB3 links:

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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
HMGXB3	NM_014983.3 linkuse as main transcript	c.310C>T	p.Pro104Ser	missense_variant, splice_region_variant	3/20	ENST00000502717.6
HMGXB3	NM_001366501.2 linkuse as main transcript	c.310C>T	p.Pro104Ser	missense_variant, splice_region_variant	3/19
HMGXB3	XM_047416963.1 linkuse as main transcript	c.310C>T	p.Pro104Ser	missense_variant, splice_region_variant	3/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
HMGXB3	ENST00000502717.6 linkuse as main transcript	c.310C>T	p.Pro104Ser	missense_variant, splice_region_variant	3/20	1	NM_014983.3	P2
HMGXB3	ENST00000613459.4 linkuse as main transcript	c.1048C>T	p.Pro350Ser	missense_variant, splice_region_variant	4/21	5		A2
HMGXB3	ENST00000503427.5 linkuse as main transcript	c.310C>T	p.Pro104Ser	missense_variant, splice_region_variant	3/21	5		A2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.15e-7

AC:

AN:

1398476

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

689704

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000280

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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 31, 2023

The c.310C>T (p.P104S) alteration is located in exon 3 (coding exon 2) of the HMGXB3 gene. This alteration results from a C to T substitution at nucleotide position 310, causing the proline (P) at amino acid position 104 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

Benign

0.23

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.40

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0015

T;T;.

Eigen

Uncertain

0.24

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.88

D;D;D

M_CAP

Benign

0.0029

MetaRNN

Benign

0.14

T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-0.14

N;.;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-1.9

.;N;N

REVEL

Benign

0.18

Sift

Benign

0.27

.;T;T

Sift4G

Benign

0.31

T;T;T

Polyphen

0.66

P;.;.

Vest4

0.19

MutPred

0.56

Gain of phosphorylation at P350 (P = 0.0519);.;.;

MVP

0.15

ClinPred

0.87

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.13

gMVP

0.51

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.79

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over