Variant 7-105614755-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_020725.2(ATXN7L1):c.1579G>A(p.Val527Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000683 in 1,551,510 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000070 ( 0 hom. )

Consequence

ATXN7L1
NM_020725.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.05

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12467566).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ATXN7L1	NM_020725.2 linkuse as main transcript	c.1579G>A	p.Val527Ile	missense_variant	10/12	ENST00000419735.8	NP_065776.1
ATXN7L1	NM_001385596.1 linkuse as main transcript	c.1579G>A	p.Val527Ile	missense_variant	10/12		NP_001372525.1
ATXN7L1	NM_138495.2 linkuse as main transcript	c.1207G>A	p.Val403Ile	missense_variant	8/10		NP_612504.1
ATXN7L1	NM_001318229.2 linkuse as main transcript	c.931G>A	p.Val311Ile	missense_variant	10/10		NP_001305158.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATXN7L1	ENST00000419735.8 linkuse as main transcript	c.1579G>A	p.Val527Ile	missense_variant	10/12	1	NM_020725.2	ENSP00000410759	P1	Q9ULK2-1

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152060

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000324

AC:

AN:

154180

Hom.:

AF XY:

0.0000245

AC XY:

AN XY:

81788

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000118

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000439

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000502

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000700

AC:

AN:

1399450

Hom.:

Cov.:

AF XY:

0.0000666

AC XY:

AN XY:

690232

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000794

Gnomad4 EAS exome

AF:

0.0000280

Gnomad4 SAS exome

AF:

0.0000379

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000834

Gnomad4 OTH exome

AF:

0.0000345

GnomAD4 genome

AF:

0.0000526

AC:

AN:

152060

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74282

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000180

Hom.:

Bravo

AF:

0.0000416

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ExAC

AF:

0.0000302

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

Jul 21, 2021

The c.1579G>A (p.V527I) alteration is located in exon 10 (coding exon 10) of the ATXN7L1 gene. This alteration results from a G to A substitution at nucleotide position 1579, causing the valine (V) at amino acid position 527 to be replaced by an isoleucine (I). 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

0.077

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.0052

T;.;T;T

Eigen

Benign

0.040

Eigen_PC

Benign

0.17

FATHMM_MKL

Benign

0.49

LIST_S2

Uncertain

0.95

D;D;D;D

M_CAP

Benign

0.0049

MetaRNN

Benign

0.12

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

L;.;.;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-0.26

N;N;N;N

REVEL

Benign

0.054

Sift

Benign

0.27

T;T;T;T

Sift4G

Benign

0.42

T;T;T;T

Polyphen

0.69

P;P;.;.

Vest4

0.19

MVP

0.45

MPC

0.40

ClinPred

0.090

GERP RS

5.7

Varity_R

0.068

gMVP

0.19

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