Genetic Variant ATXN7L1:p.Pro806Ser (chr7-105613918-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_020725.2(ATXN7L1):c.2416C>T(p.Pro806Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000121 in 1,399,796 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: not found (cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

ATXN7L1
NM_020725.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.16

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=0.11410588).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATXN7L1	NM_020725.2 link	c.2416C>T	p.Pro806Ser	missense_variant	Exon 10 of 12	ENST00000419735.8	NP_065776.1	Q9ULK2-1
ATXN7L1	NM_001385596.1 link	c.2416C>T	p.Pro806Ser	missense_variant	Exon 10 of 12		NP_001372525.1
ATXN7L1	NM_138495.2 link	c.2044C>T	p.Pro682Ser	missense_variant	Exon 8 of 10		NP_612504.1	Q9ULK2-3
ATXN7L1	NM_001318229.2 link	c.1768C>T	p.Pro590Ser	missense_variant	Exon 10 of 10		NP_001305158.1	Q9BTQ8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATXN7L1	ENST00000419735.8 link	c.2416C>T	p.Pro806Ser	missense_variant	Exon 10 of 12	1	NM_020725.2	ENSP00000410759.3		Q9ULK2-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000190

AC:

AN:

158020

Hom.:

AF XY:

0.0000240

AC XY:

AN XY:

83438

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000275

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:

0.0000121

AC:

AN:

1399796

Hom.:

Cov.:

AF XY:

0.0000174

AC XY:

AN XY:

690364

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000560

Gnomad4 SAS exome

AF:

0.000164

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.27e-7

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

Jun 23, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2416C>T (p.P806S) 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 2416, causing the proline (P) at amino acid position 806 to be replaced by a serine (S). 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

0.072

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0049

T;.;T;T

Eigen

Benign

0.022

Eigen_PC

Benign

0.18

FATHMM_MKL

Benign

0.74

LIST_S2

Uncertain

0.90

D;D;D;D

M_CAP

Benign

0.0031

MetaRNN

Benign

0.11

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.0

L;.;.;.

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.82

N;N;N;N

REVEL

Benign

0.022

Sift

Benign

0.060

T;T;D;D

Sift4G

Benign

0.50

T;T;T;T

Polyphen

0.063

B;B;.;.

Vest4

0.35

MutPred

0.20

Loss of catalytic residue at P806 (P = 0.0018);.;.;.;

MVP

0.48

MPC

0.66

ClinPred

0.11

GERP RS

4.9

Varity_R

0.073

gMVP

0.30

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