5-150041939-A-C

Variant names:

• chr5-150041939-A-C
• rs2276982
• NM_014983.3:c.2700A>C

Variant summary

Our verdict is Likely benign. The variant received -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. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. E900E) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: HMGXB3 NM_014983.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0100
• Publications: 16 publications found

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 Gene-Disease associations (from GenCC):

• Tourette syndrome

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014983.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HMGXB3	NM_014983.3	MANE Select	c.2700A>C	p.Glu900Asp	missense	Exon 15 of 20	NP_055798.3	Q12766
	HMGXB3	NM_001366501.2		c.2202A>C	p.Glu734Asp	missense	Exon 14 of 19	NP_001353430.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HMGXB3	ENST00000502717.6	TSL:1 MANE Select	c.2700A>C	p.Glu900Asp	missense	Exon 15 of 20	ENSP00000421917.1	Q12766
	HMGXB3	ENST00000613459.4	TSL:5	c.3438A>C	p.Glu1146Asp	missense	Exon 16 of 21	ENSP00000479027.1	A0A8C8PVR7
	HMGXB3	ENST00000971018.1		c.2787A>C	p.Glu929Asp	missense	Exon 16 of 21	ENSP00000641077.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000128 AC: 2 AN: 156460 AF XY: 0.00

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 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

Alfa AF: 0.00 Hom.: 6217

ExAC AF: 0.0000801 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.23
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.0080	T
MetaRNN	Benign	0.054	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.010
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.054
Sift	Benign	0.35	T
Sift4G	Benign	0.36	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
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs2276982; hg19: chr5-149421502;