3-63912809-T-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001377405.1(ATXN7):c.211T>G(p.Ser71Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000367 in 1,564,862 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00047 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00036 ( 3 hom. )

Consequence

ATXN7
NM_001377405.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.954

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006044239).

BP6

Variant 3-63912809-T-G is Benign according to our data. Variant chr3-63912809-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 208954.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 71 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATXN7	NM_001377405.1 link	c.211T>G	p.Ser71Ala	missense_variant	Exon 3 of 13	ENST00000674280.1	NP_001364334.1
ATXN7	NM_001177387.1 link	c.211T>G	p.Ser71Ala	missense_variant	Exon 2 of 13		NP_001170858.1	O15265-2
ATXN7	NM_000333.4 link	c.211T>G	p.Ser71Ala	missense_variant	Exon 3 of 13		NP_000324.1	O15265-1Q9UPD8
ATXN7	NM_001377406.1 link	c.211T>G	p.Ser71Ala	missense_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.211T>G	p.Ser71Ala	missense_variant	Exon 3 of 13		NM_001377405.1	ENSP00000501377.1		O15265-1

Frequencies

GnomAD3 genomes

AF:

0.000469

AC:

AN:

151276

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000484

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000657

Gnomad ASJ

AF:

0.0177

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000592

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000586

AC:

117

AN:

199606

Hom.:

AF XY:

0.000588

AC XY:

AN XY:

112162

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.0111

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000220

Gnomad OTH exome

AF:

0.000444

GnomAD4 exome

AF:

0.000357

AC:

504

AN:

1413586

Hom.:

Cov.:

AF XY:

0.000351

AC XY:

247

AN XY:

703216

show subpopulations

Gnomad4 AFR exome

AF:

0.000103

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0125

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000243

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000112

Gnomad4 OTH exome

AF:

0.00115

GnomAD4 genome

AF:

0.000469

AC:

AN:

151276

Hom.:

Cov.:

AF XY:

0.000393

AC XY:

AN XY:

73814

show subpopulations

Gnomad4 AFR

AF:

0.0000484

Gnomad4 AMR

AF:

0.0000657

Gnomad4 ASJ

AF:

0.0177

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000592

Gnomad4 OTH

AF:

0.00144

Alfa

AF:

0.00113

Hom.:

Bravo

AF:

0.000484

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000984

AC:

ExAC

AF:

0.000508

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Dec 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

ATXN7: BS1 -

Abnormality of neuronal migration

Benign:1

Oct 31, 2014

Génétique et pathophysiologie de maladies neurodéveloppementales et épileptogènes, Institut de génétique et de biologie moléculaire et cellulaire

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.069

.;T;.;T;.

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.59

FATHMM_MKL

Benign

0.57

LIST_S2

Benign

0.30

T;T;T;.;.

M_CAP

Benign

0.017

MetaRNN

Benign

0.0060

T;T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.69

.;N;N;N;N

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-0.14

.;N;N;N;.

REVEL

Benign

0.045

Sift

Benign

0.43

.;T;T;T;.

Sift4G

Benign

0.11

.;T;T;T;.

Polyphen

0.0010

.;B;B;B;B

Vest4

0.17, 0.18, 0.18

MVP

0.32

ClinPred

0.060

GERP RS

1.1

Varity_R

0.097

gMVP

0.14

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