3-63912871-G-C

Variant names:

Variant summary

Our verdict is Benign. Variant got -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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 1284420.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-63912871-G-C is described in Lovd as [Benign]. Variant chr3-63912871-G-C is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=1.52 with no splicing effect.

BS2

High AC in GnomAd4 at 311 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATXN7	NM_001377405.1 link	c.273G>C	p.Leu91Leu	synonymous_variant	Exon 3 of 13	ENST00000674280.1	NP_001364334.1
ATXN7	NM_001177387.1 link	c.273G>C	p.Leu91Leu	synonymous_variant	Exon 2 of 13		NP_001170858.1	O15265-2
ATXN7	NM_000333.4 link	c.273G>C	p.Leu91Leu	synonymous_variant	Exon 3 of 13		NP_000324.1	O15265-1Q9UPD8
ATXN7	NM_001377406.1 link	c.273G>C	p.Leu91Leu	synonymous_variant	Exon 2 of 12		NP_001364335.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATXN7	ENST00000674280.1 link	c.273G>C	p.Leu91Leu	synonymous_variant	Exon 3 of 13		NM_001377405.1	ENSP00000501377.1		O15265-1

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

GnomAD3 exomes

AF:

0.00165

AC:

404

AN:

245476

Hom.:

AF XY:

0.00163

AC XY:

218

AN XY:

134114

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 SAS exome

AF:

0.0000981

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

Gnomad4 AFR exome

AF:

0.000388

Gnomad4 AMR exome

AF:

0.000671

Gnomad4 ASJ exome

AF:

0.000191

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000696

Gnomad4 FIN exome

AF:

0.00224

Gnomad4 NFE exome

AF:

0.00302

Gnomad4 OTH exome

AF:

0.00215

GnomAD4 genome

AF:

0.00205

AC:

311

AN:

151934

Hom.:

Cov.:

AF XY:

0.00183

AC XY:

136

AN XY:

74258

show subpopulations

Gnomad4 AFR

AF:

0.000385

Gnomad4 AMR

AF:

0.000785

Gnomad4 ASJ

AF:

0.000578

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00208

Gnomad4 NFE

AF:

0.00379

Gnomad4 OTH

AF:

0.000950

Alfa

AF:

0.00276

Hom.:

Bravo

AF:

0.00165

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

ATXN7: BS1, BS2 -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not specified

Benign:1

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.82

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over