NM_014983.3:c.5A>G

Variant names:

• chr5-150004857-A-G
• rs1312619257
• NM_014983.3:c.5A>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.5A>G​(p.Asp2Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000131 in 152,210 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: 𝑓 0.000013 (0 hom., cov: 33)
• Consequence: HMGXB3 NM_014983.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.03
• Publications: 2 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=0.18582037).

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.5A>G	p.Asp2Gly	missense	Exon 2 of 20	NP_055798.3	Q12766
	HMGXB3	NM_001366501.2		c.5A>G	p.Asp2Gly	missense	Exon 2 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.5A>G	p.Asp2Gly	missense	Exon 2 of 20	ENSP00000421917.1	Q12766
	HMGXB3	ENST00000613459.4	TSL:5	c.743A>G	p.Asp248Gly	missense	Exon 3 of 21	ENSP00000479027.1	A0A8C8PVR7
	HMGXB3	ENST00000971018.1		c.5A>G	p.Asp2Gly	missense	Exon 2 of 21	ENSP00000641077.1

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152210 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 29

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152210 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74356

African (AFR) AF: 0.00 AC: 0 AN: 41436

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5204

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68044

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000189

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	0.18
BayesDel_addAF	Uncertain	0.014	T
BayesDel_noAF	Benign	-0.22
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0069	T
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.0078	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.81	L
PhyloP100		4.0
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-2.2	N
REVEL	Uncertain	0.43
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.016	D
Polyphen		0.94	P
Vest4		0.49
MutPred		0.29		Gain of catalytic residue at D248 (P = 0.047)
MVP		0.12
ClinPred		0.86	D
GERP RS		5.5
Varity_R		0.24
gMVP		0.48
Mutation Taster		=72/28	polymorphism

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: rs1312619257; hg19: chr5-149384420;