Variant 7-105610533-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_020725.2(ATXN7L1):c.2543G>A(p.Arg848Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000571 in 1,550,706 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00055 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00057 ( 0 hom. )

Consequence

ATXN7L1
NM_020725.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.12

Variant links:

Genes affected

ATXN7L1 (HGNC:22210): (ataxin 7 like 1)

ATXN7L1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.021879971).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ATXN7L1	NM_020725.2 linkuse as main transcript	c.2543G>A	p.Arg848Gln	missense_variant	11/12	ENST00000419735.8	NP_065776.1
ATXN7L1	NM_001385596.1 linkuse as main transcript	c.2543G>A	p.Arg848Gln	missense_variant	11/12		NP_001372525.1
ATXN7L1	NM_138495.2 linkuse as main transcript	c.2171G>A	p.Arg724Gln	missense_variant	9/10		NP_612504.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATXN7L1	ENST00000419735.8 linkuse as main transcript	c.2543G>A	p.Arg848Gln	missense_variant	11/12	1	NM_020725.2	ENSP00000410759	P1	Q9ULK2-1
ATXN7L1	ENST00000477775.5 linkuse as main transcript	c.2171G>A	p.Arg724Gln	missense_variant	9/10	2		ENSP00000418476		Q9ULK2-3

Frequencies

GnomAD3 genomes

AF:

0.000546

AC:

AN:

151932

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000339

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000624

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.000779

Gnomad OTH

AF:

0.000959

GnomAD3 exomes

AF:

0.000468

AC:

AN:

156130

Hom.:

AF XY:

0.000338

AC XY:

AN XY:

82748

show subpopulations

Gnomad AFR exome

AF:

0.000253

Gnomad AMR exome

AF:

0.000610

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000220

Gnomad FIN exome

AF:

0.0000595

Gnomad NFE exome

AF:

0.000779

Gnomad OTH exome

AF:

0.000685

GnomAD4 exome

AF:

0.000574

AC:

803

AN:

1398654

Hom.:

Cov.:

AF XY:

0.000589

AC XY:

406

AN XY:

689866

show subpopulations

Gnomad4 AFR exome

AF:

0.000222

Gnomad4 AMR exome

AF:

0.000534

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000594

Gnomad4 FIN exome

AF:

0.0000609

Gnomad4 NFE exome

AF:

0.000632

Gnomad4 OTH exome

AF:

0.000673

GnomAD4 genome

AF:

0.000546

AC:

AN:

152052

Hom.:

Cov.:

AF XY:

0.000498

AC XY:

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.000338

Gnomad4 AMR

AF:

0.000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000625

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000780

Gnomad4 OTH

AF:

0.000949

Alfa

AF:

0.000608

Hom.:

Bravo

AF:

0.000521

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000943

AC:

ExAC

AF:

0.000656

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 01, 2021

The c.2543G>A (p.R848Q) alteration is located in exon 11 (coding exon 11) of the ATXN7L1 gene. This alteration results from a G to A substitution at nucleotide position 2543, causing the arginine (R) at amino acid position 848 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.43

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0047

T;.

Eigen

Uncertain

0.32

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.71

T;D

M_CAP

Benign

0.0069

MetaRNN

Benign

0.022

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

L;.

MutationTaster

Benign

0.57

D;N

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.55

N;N

REVEL

Benign

0.11

Sift

Benign

0.048

D;D

Sift4G

Benign

0.36

T;T

Polyphen

0.90

P;D

Vest4

0.43

MVP

0.46

MPC

0.53

ClinPred

0.034

GERP RS

5.4

Varity_R

0.099

gMVP

0.58

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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