Variant 7-105614770-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000419735.8(ATXN7L1):c.1564C>T(p.His522Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000286 in 1,399,418 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000029 ( 0 hom. )

Consequence

ATXN7L1
ENST00000419735.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.89

Variant links:

Genes affected

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

ATXN7L1 links:

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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=0.19009021).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ATXN7L1	NM_020725.2 linkuse as main transcript	c.1564C>T	p.His522Tyr	missense_variant	10/12	ENST00000419735.8	NP_065776.1
ATXN7L1	NM_001385596.1 linkuse as main transcript	c.1564C>T	p.His522Tyr	missense_variant	10/12		NP_001372525.1
ATXN7L1	NM_138495.2 linkuse as main transcript	c.1192C>T	p.His398Tyr	missense_variant	8/10		NP_612504.1
ATXN7L1	NM_001318229.2 linkuse as main transcript	c.916C>T	p.His306Tyr	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.1564C>T	p.His522Tyr	missense_variant	10/12	1	NM_020725.2	ENSP00000410759	P1	Q9ULK2-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000260

AC:

AN:

153952

Hom.:

AF XY:

0.0000245

AC XY:

AN XY:

81660

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000162

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000286

AC:

AN:

1399418

Hom.:

Cov.:

AF XY:

0.00000290

AC XY:

AN XY:

690222

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000112

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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 20, 2023

The c.1564C>T (p.H522Y) alteration is located in exon 10 (coding exon 10) of the ATXN7L1 gene. This alteration results from a C to T substitution at nucleotide position 1564, causing the histidine (H) at amino acid position 522 to be replaced by a tyrosine (Y). 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

0.12

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.31

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

T;.;T;T

Eigen

Benign

0.19

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Uncertain

0.83

LIST_S2

Uncertain

0.95

D;D;D;D

M_CAP

Benign

0.0078

MetaRNN

Benign

0.19

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

M;.;.;.

MutationTaster

Benign

0.55

D;D;N

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-2.3

N;N;N;N

REVEL

Benign

0.10

Sift

Benign

0.040

D;D;D;D

Sift4G

Uncertain

0.060

T;T;T;T

Polyphen

0.17

B;B;.;.

Vest4

0.40

MutPred

0.31

Gain of phosphorylation at H522 (P = 0.0267);.;.;.;

MVP

0.51

MPC

0.64

ClinPred

0.25

GERP RS

5.7

Varity_R

0.23

gMVP

0.58

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