dbSNP rs201334618: ATXN7:p.Leu91Leu (chr3-63912871-G-C) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001377405.1(ATXN7):c.273G>C(p.Leu91Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00247 in 1,613,414 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0020 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0025 ( 10 hom. )

Consequence

ATXN7
NM_001377405.1 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:3

Conservation

PhyloP100: 1.52

Publications

1 publications found

Variant links:

Genes affected

ATXN7 (HGNC:10560): (ataxin 7) The autosomal dominant cerebellar ataxias (ADCA) are a heterogeneous group of neurodegenerative disorders characterized by progressive degeneration of the cerebellum, brain stem and spinal cord. Clinically, ADCA has been divided into three groups: ADCA types I-III. ADCAI is genetically heterogeneous, with five genetic loci, designated spinocerebellar ataxia (SCA) 1, 2, 3, 4 and 6, being assigned to five different chromosomes. ADCAII, which always presents with retinal degeneration (SCA7), and ADCAIII often referred to as the 'pure' cerebellar syndrome (SCA5), are most likely homogeneous disorders. Several SCA genes have been cloned and shown to contain CAG repeats in their coding regions. ADCA is caused by the expansion of the CAG repeats, producing an elongated polyglutamine tract in the corresponding protein. The expanded repeats are variable in size and unstable, usually increasing in size when transmitted to successive generations. This locus has been mapped to chromosome 3, and it has been determined that the diseased allele associated with spinocerebellar ataxia-7 contains 37-306 CAG repeats (near the N-terminus), compared to 4-35 in the normal allele. The encoded protein is a component of the SPT3/TAF9/GCN5 acetyltransferase (STAGA) and TBP-free TAF-containing (TFTC) chromatin remodeling complexes, and it thus plays a role in transcriptional regulation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2016]

ATXN7 Gene-Disease associations (from GenCC):

spinocerebellar ataxia 7
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
spinocerebellar ataxia type 7
Inheritance: AD Classification: MODERATE, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics

ATXN7 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

Variant 3-63912871-G-C is Benign according to our data. Variant chr3-63912871-G-C is described in ClinVar as Benign. ClinVar VariationId is 1284420.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=1.52 with no splicing effect.

BS2

High AC in GnomAd4 at 311 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001377405.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ATXN7	NM_001377405.1	MANE Select	c.273G>C	p.Leu91Leu	synonymous	Exon 3 of 13	NP_001364334.1	O15265-1
ATXN7	NM_001177387.1		c.273G>C	p.Leu91Leu	synonymous	Exon 2 of 13	NP_001170858.1	O15265-2
ATXN7	NM_000333.4		c.273G>C	p.Leu91Leu	synonymous	Exon 3 of 13	NP_000324.1	O15265-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ATXN7	ENST00000674280.1	MANE Select	c.273G>C	p.Leu91Leu	synonymous	Exon 3 of 13	ENSP00000501377.1	O15265-1
ATXN7	ENST00000295900.10	TSL:1	c.273G>C	p.Leu91Leu	synonymous	Exon 3 of 13	ENSP00000295900.6	O15265-1
ATXN7	ENST00000522345.2	TSL:2	c.273G>C	p.Leu91Leu	synonymous	Exon 1 of 12	ENSP00000428067.2	O15265-2

Frequencies

GnomAD3 genomes

AF:

0.00205

AC:

312

AN:

151826

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000411

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000786

Gnomad ASJ

AF:

0.000578

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00208

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00379

Gnomad OTH

AF:

0.000960

GnomAD2 exomes

AF:

0.00165

AC:

404

AN:

245476

AF XY:

0.00163

show subpopulations

Gnomad AFR exome

AF:

0.000523

Gnomad AMR exome

AF:

0.000638

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00186

Gnomad NFE exome

AF:

0.00295

Gnomad OTH exome

AF:

0.00116

GnomAD4 exome

AF:

0.00251

AC:

3668

AN:

1461480

Hom.:

Cov.:

AF XY:

0.00243

AC XY:

1768

AN XY:

727074

show subpopulations

African (AFR)

AF:

0.000388

AC:

AN:

33474

American (AMR)

AF:

0.000671

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.000191

AC:

AN:

26128

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.0000696

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.00224

AC:

119

AN:

53210

Middle Eastern (MID)

AF:

0.000869

AC:

AN:

5752

European-Non Finnish (NFE)

AF:

0.00302

AC:

3360

AN:

1111882

Other (OTH)

AF:

0.00215

AC:

130

AN:

60368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

198

395

593

790

988

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

114

228

342

456

570

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00205

AC:

311

AN:

151934

Hom.:

Cov.:

AF XY:

0.00183

AC XY:

136

AN XY:

74258

show subpopulations

African (AFR)

AF:

0.000385

AC:

AN:

41526

American (AMR)

AF:

0.000785

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.000578

AC:

AN:

3458

East Asian (EAS)

AF:

0.00

AC:

AN:

5110

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00208

AC:

AN:

10570

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00379

AC:

257

AN:

67850

Other (OTH)

AF:

0.000950

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00276

Hom.:

Bravo

AF:

0.00165

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Benign

0.82

PhyloP100

1.5

PromoterAI

-0.039

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over