rs868854400

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001377405.1(ATXN7):c.116A>C(p.Gln39Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00041 in 1,212,584 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.00029 ( 1 hom., cov: 31)

Exomes 𝑓: 0.00043 ( 0 hom. )

Consequence

ATXN7
NM_001377405.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 0.00

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012874275).

BS2

High AC in GnomAd4 at 43 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATXN7	NM_001377405.1 link	c.116A>C	p.Gln39Pro	missense_variant	Exon 3 of 13	ENST00000674280.1	NP_001364334.1
ATXN7	NM_001177387.1 link	c.116A>C	p.Gln39Pro	missense_variant	Exon 2 of 13		NP_001170858.1	O15265-2
ATXN7	NM_000333.4 link	c.116A>C	p.Gln39Pro	missense_variant	Exon 3 of 13		NP_000324.1	O15265-1Q9UPD8
ATXN7	NM_001377406.1 link	c.116A>C	p.Gln39Pro	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.116A>C	p.Gln39Pro	missense_variant	Exon 3 of 13		NM_001377405.1	ENSP00000501377.1		O15265-1

Frequencies

GnomAD3 genomes

AF:

0.000293

AC:

AN:

146898

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000223

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000202

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000415

Gnomad SAS

AF:

0.00336

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000181

Gnomad OTH

AF:

0.000494

GnomAD3 exomes

AF:

0.000935

AC:

AN:

32074

Hom.:

AF XY:

0.000938

AC XY:

AN XY:

18122

show subpopulations

Gnomad AFR exome

AF:

0.00365

Gnomad AMR exome

AF:

0.000841

Gnomad ASJ exome

AF:

0.00114

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00112

Gnomad FIN exome

AF:

0.000567

Gnomad NFE exome

AF:

0.00103

Gnomad OTH exome

AF:

0.00272

GnomAD4 exome

AF:

0.000426

AC:

454

AN:

1065578

Hom.:

Cov.:

AF XY:

0.000458

AC XY:

234

AN XY:

510578

show subpopulations

Gnomad4 AFR exome

AF:

0.000526

Gnomad4 AMR exome

AF:

0.000873

Gnomad4 ASJ exome

AF:

0.000527

Gnomad4 EAS exome

AF:

0.00167

Gnomad4 SAS exome

AF:

0.00162

Gnomad4 FIN exome

AF:

0.000190

Gnomad4 NFE exome

AF:

0.000345

Gnomad4 OTH exome

AF:

0.000695

GnomAD4 genome

AF:

0.000293

AC:

AN:

147006

Hom.:

Cov.:

AF XY:

0.000377

AC XY:

AN XY:

71544

show subpopulations

Gnomad4 AFR

AF:

0.000223

Gnomad4 AMR

AF:

0.000202

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000416

Gnomad4 SAS

AF:

0.00336

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000181

Gnomad4 OTH

AF:

0.000488

Alfa

AF:

0.000211

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Uncertain:2

Jun 01, 2016

CeGaT Center for Human Genetics Tuebingen

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.63

DEOGEN2

Benign

0.10

.;T;.;T;.

Eigen

Benign

-0.60

Eigen_PC

Benign

-0.66

FATHMM_MKL

Benign

0.72

LIST_S2

Benign

0.20

T;T;T;.;.

M_CAP

Benign

0.013

MetaRNN

Benign

0.013

T;T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.69

.;N;N;N;N

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-0.43

.;N;N;N;.

REVEL

Benign

0.042

Sift

Benign

0.35

.;T;T;T;.

Sift4G

Benign

0.094

.;T;T;T;.

Vest4

0.25, 0.24, 0.28

MVP

0.19

ClinPred

0.0080

Varity_R

0.15

gMVP

0.26

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