5-150006635-A-T

Position:

• chr5-150006635-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014983.3(HMGXB3):​c.300A>T​(p.Glu100Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: HMGXB3 NM_014983.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.18

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]

ACMG classification

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=0.1712574).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HMGXB3	NM_014983.3	c.300A>T	p.Glu100Asp	missense_variant	3/20	ENST00000502717.6
HMGXB3	NM_001366501.2	c.300A>T	p.Glu100Asp	missense_variant	3/19
HMGXB3	XM_047416963.1	c.300A>T	p.Glu100Asp	missense_variant	3/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HMGXB3	ENST00000502717.6	c.300A>T	p.Glu100Asp	missense_variant	3/20	1	NM_014983.3	P2
HMGXB3	ENST00000613459.4	c.1038A>T	p.Glu346Asp	missense_variant	4/21	5		A2
HMGXB3	ENST00000503427.5	c.300A>T	p.Glu100Asp	missense_variant	3/21	5		A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 21, 2022

The c.300A>T (p.E100D) alteration is located in exon 3 (coding exon 2) of the HMGXB3 gene. This alteration results from a A to T substitution at nucleotide position 300, causing the glutamic acid (E) at amino acid position 100 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	0.29
BayesDel_addAF	Uncertain	0.065	T
BayesDel_noAF	Benign	-0.14
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0024	T;T;.
Eigen	Benign	0.13
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Uncertain	0.87	D;D;D
M_CAP	Benign	0.049	D
MetaRNN	Benign	0.17	T;T;T
MetaSVM	Uncertain	0.44	D
MutationAssessor	Benign	0.67	N;.;.
MutationTaster	Benign	0.99	D;D
PrimateAI	Uncertain	0.70	T
Sift4G	Benign	0.52	T;T;T
Polyphen		0.59	P;.;.
Vest4		0.20
MutPred		0.46		Gain of loop (P = 0.0435);.;.;
MVP		0.35
ClinPred		0.70	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.34
gMVP		0.57

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

Other links and lift over

dbSNP: rs542202858; hg19: chr5-149386198;