rs1561851416

Variant names:

• chr5-150010370-A-G
• rs1561851416
• NM_014983.3:c.572A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014983.3(HMGXB3):​c.572A>G​(p.Glu191Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000143 in 1,399,400 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: HMGXB3 NM_014983.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.57
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17844832).

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.572A>G	p.Glu191Gly	missense	Exon 4 of 20	NP_055798.3	Q12766
	HMGXB3	NM_001366501.2		c.313-1885A>G		intron	N/A	NP_001353430.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HMGXB3	ENST00000502717.6	TSL:1 MANE Select	c.572A>G	p.Glu191Gly	missense	Exon 4 of 20	ENSP00000421917.1	Q12766
	HMGXB3	ENST00000613459.4	TSL:5	c.1310A>G	p.Glu437Gly	missense	Exon 5 of 21	ENSP00000479027.1	A0A8C8PVR7
	HMGXB3	ENST00000971018.1		c.572A>G	p.Glu191Gly	missense	Exon 4 of 21	ENSP00000641077.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000143 AC: 2 AN: 1399400 Hom.: 0 Cov.: 32 AF XY: 0.00000145 AC XY: 1 AN XY: 690208

African (AFR) AF: 0.00 AC: 0 AN: 31598

American (AMR) AF: 0.00 AC: 0 AN: 35702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25182

East Asian (EAS) AF: 0.0000560 AC: 2 AN: 35738

South Asian (SAS) AF: 0.00 AC: 0 AN: 79236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49268

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078974

Other (OTH) AF: 0.00 AC: 0 AN: 58004

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Uncertain	0.029	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.013	T
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.0078	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	0.90	L
PhyloP100		6.6
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.24
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.021	D
Polyphen		0.68	P
Vest4		0.14
MutPred		0.23		Gain of loop (P = 0.0051)
MVP		0.28
ClinPred		0.89	D
GERP RS		5.9
Varity_R		0.49
gMVP		0.65
Mutation Taster		=48/52	disease causing

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: rs1561851416; hg19: chr5-149389933;