NM_014983.3:c.1983+612A>G

Variant names:

• chr5-150033215-A-G
• rs6890492
• NM_014983.3:c.1983+612A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014983.3(HMGXB3):​c.1983+612A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 152,032 control chromosomes in the GnomAD database, including 2,631 homozygotes. 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: 𝑓 0.17 (2631 hom., cov: 31)
• Consequence: HMGXB3 NM_014983.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.10
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.265 is higher than 0.05.

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.1983+612A>G		intron	N/A	NP_055798.3	Q12766
	HMGXB3	NM_001366501.2		c.1485+612A>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.1983+612A>G		intron	N/A	ENSP00000421917.1	Q12766
	HMGXB3	ENST00000613459.4	TSL:5	c.2721+612A>G		intron	N/A	ENSP00000479027.1	A0A8C8PVR7
	HMGXB3	ENST00000971018.1		c.2070+612A>G		intron	N/A	ENSP00000641077.1

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25418 AN: 151914 Hom.: 2628 Cov.: 31

Gnomad AFR AF: 0.268

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.272

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.104

Gnomad SAS AF: 0.0408

Gnomad FIN AF: 0.0904

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.178

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.167 AC: 25448 AN: 152032 Hom.: 2631 Cov.: 31 AF XY: 0.167 AC XY: 12389 AN XY: 74344

African (AFR) AF: 0.268 AC: 11096 AN: 41428

American (AMR) AF: 0.272 AC: 4149 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.145 AC: 503 AN: 3472

East Asian (EAS) AF: 0.104 AC: 538 AN: 5174

South Asian (SAS) AF: 0.0404 AC: 195 AN: 4824

European-Finnish (FIN) AF: 0.0904 AC: 957 AN: 10590

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.110 AC: 7458 AN: 67968

Other (OTH) AF: 0.176 AC: 371 AN: 2108

Alfa AF: 0.105 Hom.: 232

Bravo AF: 0.189

Asia WGS AF: 0.0910 AC: 320 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.020
DANN	Benign	0.67
PhyloP100		-3.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs6890492; hg19: chr5-149412778;