5-150045403-G-T

Variant names:

• chr5-150045403-G-T
• rs2276983
• NM_014983.3:c.2731-63G>T

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.2731-63G>T variant causes a intron 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HMGXB3 NM_014983.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.492
• Publications: 5 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 (BayesDel_noAF=-0.83).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HMGXB3	NM_014983.3	MANE Select	c.2731-63G>T		intron	N/A	NP_055798.3
	HMGXB3	NM_001366501.2		c.2233-63G>T		intron	N/A	NP_001353430.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HMGXB3	ENST00000502717.6	TSL:1 MANE Select	c.2731-63G>T		intron	N/A	ENSP00000421917.1
	HMGXB3	ENST00000613459.4	TSL:5	c.3469-63G>T		intron	N/A	ENSP00000479027.1
	HMGXB3	ENST00000503427.5	TSL:5	c.2635-63G>T		intron	N/A	ENSP00000422231.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1157982 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 581372

African (AFR) AF: 0.00 AC: 0 AN: 26794

American (AMR) AF: 0.00 AC: 0 AN: 35220

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23468

East Asian (EAS) AF: 0.00 AC: 0 AN: 34510

South Asian (SAS) AF: 0.00 AC: 0 AN: 73740

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48728

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5216

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 860444

Other (OTH) AF: 0.00 AC: 0 AN: 49862

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 9377

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.066
DANN	Benign	0.32
PhyloP100		-0.49

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2276983; hg19: chr5-149424966;