rs2276982

Positions:

• chr5-150041939-A-C
• chr5-150041939-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014983.3(HMGXB3):​c.2700A>C​(p.Glu900Asp) 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. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: HMGXB3 NM_014983.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0100

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05369872).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HMGXB3	NM_014983.3	c.2700A>C	p.Glu900Asp	missense_variant	15/20	ENST00000502717.6	NP_055798.3
HMGXB3	NM_001366501.2	c.2202A>C	p.Glu734Asp	missense_variant	14/19		NP_001353430.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HMGXB3	ENST00000502717.6	c.2700A>C	p.Glu900Asp	missense_variant	15/20	1	NM_014983.3	ENSP00000421917.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000128 AC: 2 AN: 156460 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 82914

Gnomad AFR exome AF: 0.000252

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 Cov.: 32

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000801 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0039	T;T;.
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.23
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Uncertain	0.92	D;D;D
M_CAP	Benign	0.0080	T
MetaRNN	Benign	0.054	T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.4	L;.;.
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.1	.;N;N
REVEL	Benign	0.054
Sift	Benign	0.35	.;T;T
Sift4G	Benign	0.36	T;T;T
Polyphen		0.72	P;.;.
Vest4		0.19
MutPred		0.42		Gain of loop (P = 0.0079);.;.;
MVP		0.12
ClinPred		0.17	T
GERP RS		0.95
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.046
gMVP		0.48

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: rs2276982; hg19: chr5-149421502;