Variant chr7-105614593-T-C 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.1741A>G(p.Thr581Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000158 in 1,551,518 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00016 ( 0 hom. )

Consequence

ATXN7L1
NM_020725.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.260

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=0.04082188).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATXN7L1	NM_020725.2 linkuse as main transcript	c.1741A>G	p.Thr581Ala	missense_variant	10/12	ENST00000419735.8	NP_065776.1	Q9ULK2-1
ATXN7L1	NM_001385596.1 linkuse as main transcript	c.1741A>G	p.Thr581Ala	missense_variant	10/12		NP_001372525.1
ATXN7L1	NM_138495.2 linkuse as main transcript	c.1369A>G	p.Thr457Ala	missense_variant	8/10		NP_612504.1	Q9ULK2-3
ATXN7L1	NM_001318229.2 linkuse as main transcript	c.1093A>G	p.Thr365Ala	missense_variant	10/10		NP_001305158.1	Q9BTQ8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATXN7L1	ENST00000419735.8 linkuse as main transcript	c.1741A>G	p.Thr581Ala	missense_variant	10/12	1	NM_020725.2	ENSP00000410759.3		Q9ULK2-1

Frequencies

GnomAD3 genomes

AF:

0.000151

AC:

AN:

151940

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

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:

0.0000883

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000762

AC:

AN:

157424

Hom.:

AF XY:

0.0000601

AC XY:

AN XY:

83192

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000243

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000981

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000159

AC:

222

AN:

1399578

Hom.:

Cov.:

AF XY:

0.000164

AC XY:

113

AN XY:

690280

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000252

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000195

Gnomad4 OTH exome

AF:

0.0000516

GnomAD4 genome

AF:

0.000151

AC:

AN:

151940

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74196

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000883

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000113

Hom.:

Bravo

AF:

0.000178

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

Mar 20, 2023

The c.1741A>G (p.T581A) alteration is located in exon 10 (coding exon 10) of the ATXN7L1 gene. This alteration results from a A to G substitution at nucleotide position 1741, causing the threonine (T) at amino acid position 581 to be replaced by an alanine (A). 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

0.062

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.74

DEOGEN2

Benign

0.0028

T;.;T;T

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.31

FATHMM_MKL

Benign

0.67

LIST_S2

Benign

0.76

T;T;T;T

M_CAP

Benign

0.0043

MetaRNN

Benign

0.041

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

L;.;.;.

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-0.48

N;N;N;N

REVEL

Benign

0.032

Sift

Benign

1.0

T;T;T;T

Sift4G

Benign

0.46

T;T;T;T

Polyphen

0.14

B;B;.;.

Vest4

0.23

MutPred

0.24

Loss of glycosylation at T581 (P = 0.0368);.;.;.;

MVP

0.36

MPC

0.40

ClinPred

0.017

GERP RS

0.14

Varity_R

0.039

gMVP

0.52

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