rs910369

Variant names:

• chr14-92063938-C-A
• rs910369
• NM_004993.6:c.*382G>T

Your query was ambiguous. Multiple possible variants found:

• chr14-92063938-C-A
• chr14-92063938-C-G
• chr14-92063938-C-T

Variant summary

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

The NM_004993.6(ATXN3):​c.*382G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 158,982 control chromosomes in the GnomAD database, including 5,581 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 0.26 (5390 hom., cov: 32)
  • Exomes 𝑓: 0.22 (191 hom.)
• Consequence: ATXN3 NM_004993.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.404
• Publications: 20 publications found

Genes affected

ATXN3 (HGNC:7106): (ataxin 3) Machado-Joseph disease, also known as spinocerebellar ataxia-3, is an autosomal dominant neurologic disorder. The protein encoded by this gene contains (CAG)n repeats in the coding region, and the expansion of these repeats from the normal 12-44 to 52-86 is one cause of Machado-Joseph disease. There is a negative correlation between the age of onset and CAG repeat numbers. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jul 2016]

ATXN3 Gene-Disease associations (from GenCC):

• Machado-Joseph disease

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine
• Machado-Joseph disease type 1

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Machado-Joseph disease type 2

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Machado-Joseph disease type 3

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000303901 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.342 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004993.6. 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
	ATXN3	NM_004993.6	MANE Select	c.*382G>T		3_prime_UTR	Exon 11 of 11	NP_004984.2
	ATXN3	NM_001127696.2		c.*382G>T		3_prime_UTR	Exon 10 of 10	NP_001121168.1	P54252-4
	ATXN3	NM_001127697.3		c.*382G>T		3_prime_UTR	Exon 9 of 9	NP_001121169.2	A0A0A0MS38

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATXN3	ENST00000644486.2	MANE Select	c.*382G>T		3_prime_UTR	Exon 11 of 11	ENSP00000496695.1	P54252-2
	ATXN3	ENST00000393287.9	TSL:1	c.*382G>T		3_prime_UTR	Exon 9 of 9	ENSP00000376965.6	A0A0A0MS38
	ATXN3	ENST00000429774.6	TSL:1	c.*382G>T		3_prime_UTR	Exon 9 of 9	ENSP00000389376.3	C9JQV6

Frequencies

GnomAD3 genomes AF: 0.262 AC: 39826 AN: 151826 Hom.: 5374 Cov.: 32

Gnomad AFR AF: 0.310

Gnomad AMI AF: 0.250

Gnomad AMR AF: 0.187

Gnomad ASJ AF: 0.312

Gnomad EAS AF: 0.355

Gnomad SAS AF: 0.351

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.283

Gnomad NFE AF: 0.239

Gnomad OTH AF: 0.252

GnomAD4 exome AF: 0.219 AC: 1542 AN: 7038 Hom.: 191 Cov.: 0 AF XY: 0.228 AC XY: 832 AN XY: 3656

African (AFR) AF: 0.321 AC: 18 AN: 56

American (AMR) AF: 0.115 AC: 70 AN: 608

Ashkenazi Jewish (ASJ) AF: 0.346 AC: 36 AN: 104

East Asian (EAS) AF: 0.351 AC: 87 AN: 248

South Asian (SAS) AF: 0.287 AC: 188 AN: 654

European-Finnish (FIN) AF: 0.226 AC: 86 AN: 380

Middle Eastern (MID) AF: 0.300 AC: 3 AN: 10

European-Non Finnish (NFE) AF: 0.211 AC: 985 AN: 4658

Other (OTH) AF: 0.216 AC: 69 AN: 320

GnomAD4 genome AF: 0.262 AC: 39878 AN: 151944 Hom.: 5390 Cov.: 32 AF XY: 0.263 AC XY: 19512 AN XY: 74290

African (AFR) AF: 0.311 AC: 12885 AN: 41436

American (AMR) AF: 0.186 AC: 2847 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.312 AC: 1084 AN: 3470

East Asian (EAS) AF: 0.356 AC: 1842 AN: 5176

South Asian (SAS) AF: 0.350 AC: 1687 AN: 4822

European-Finnish (FIN) AF: 0.233 AC: 2450 AN: 10522

Middle Eastern (MID) AF: 0.281 AC: 82 AN: 292

European-Non Finnish (NFE) AF: 0.239 AC: 16240 AN: 67932

Other (OTH) AF: 0.253 AC: 533 AN: 2108

Alfa AF: 0.232 Hom.: 5690

Bravo AF: 0.260

Asia WGS AF: 0.359 AC: 1248 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.40
DANN	Benign	0.35
PhyloP100		-0.40
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: rs910369; hg19: chr14-92530282; COSMIC: COSV105232966; COSMIC: COSV105232966;