Genetic Variant NM_020725.2:c.2543G>A (chr7-105610533-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_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. 13/22 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

Publications

2 publications found

Variant links:

Genes affected

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

ATXN7L1 links:

ENSG00000295921 (HGNC:):

ENSG00000295921 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020725.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ATXN7L1	NM_020725.2	MANE Select	c.2543G>A	p.Arg848Gln	missense	Exon 11 of 12	NP_065776.1	Q9ULK2-1
ATXN7L1	NM_001385596.1		c.2543G>A	p.Arg848Gln	missense	Exon 11 of 12	NP_001372525.1
ATXN7L1	NM_138495.2		c.2171G>A	p.Arg724Gln	missense	Exon 9 of 10	NP_612504.1	Q9ULK2-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ATXN7L1	ENST00000419735.8	TSL:1 MANE Select	c.2543G>A	p.Arg848Gln	missense	Exon 11 of 12	ENSP00000410759.3	Q9ULK2-1
ATXN7L1	ENST00000477775.5	TSL:2	c.2171G>A	p.Arg724Gln	missense	Exon 9 of 10	ENSP00000418476.1	Q9ULK2-3
ENSG00000295921	ENST00000733939.1		n.109-27199C>T		intron	N/A

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

GnomAD2 exomes

AF:

0.000468

AC:

AN:

156130

AF XY:

0.000338

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 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

African (AFR)

AF:

0.000222

AC:

AN:

31576

American (AMR)

AF:

0.000534

AC:

AN:

35610

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25176

East Asian (EAS)

AF:

0.00

AC:

AN:

35722

South Asian (SAS)

AF:

0.000594

AC:

AN:

79160

European-Finnish (FIN)

AF:

0.0000609

AC:

AN:

49256

Middle Eastern (MID)

AF:

0.00105

AC:

AN:

5690

European-Non Finnish (NFE)

AF:

0.000632

AC:

682

AN:

1078496

Other (OTH)

AF:

0.000673

AC:

AN:

57968

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.440

Heterozygous variant carriers

107

142

178

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

104

130

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000546

AC:

AN:

152052

Hom.:

Cov.:

AF XY:

0.000498

AC XY:

AN XY:

74320

show subpopulations

African (AFR)

AF:

0.000338

AC:

AN:

41446

American (AMR)

AF:

0.000655

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.000625

AC:

AN:

4802

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10588

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000780

AC:

AN:

67986

Other (OTH)

AF:

0.000949

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000614

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

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.43

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0047

Eigen

Uncertain

0.32

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.71

M_CAP

Benign

0.0069

MetaRNN

Benign

0.022

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

PhyloP100

3.1

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.55

REVEL

Benign

0.11

Sift

Benign

0.048

Sift4G

Benign

0.36

Polyphen

0.90

Vest4

0.43

MVP

0.46

MPC

0.53

ClinPred

0.034

GERP RS

5.4

Varity_R

0.099

gMVP

0.58

Mutation Taster

=92/8

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over