Genetic Variant NM_020725.2:c.2492T>C (chr7-105610584-A-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_020725.2(ATXN7L1):c.2492T>C(p.Leu831Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000193 in 1,551,168 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

ATXN7L1
NM_020725.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.34

Publications

0 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: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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.2492T>C	p.Leu831Pro	missense	Exon 11 of 12	NP_065776.1	Q9ULK2-1
ATXN7L1	NM_001385596.1		c.2492T>C	p.Leu831Pro	missense	Exon 11 of 12	NP_001372525.1
ATXN7L1	NM_138495.2		c.2120T>C	p.Leu707Pro	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.2492T>C	p.Leu831Pro	missense	Exon 11 of 12	ENSP00000410759.3	Q9ULK2-1
ATXN7L1	ENST00000477775.5	TSL:2	c.2120T>C	p.Leu707Pro	missense	Exon 9 of 10	ENSP00000418476.1	Q9ULK2-3
ENSG00000295921	ENST00000733939.1		n.109-27148A>G		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151792

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000485

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000639

AC:

AN:

156494

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.000126

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS 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:

7.15e-7

AC:

AN:

1399376

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

690198

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31596

American (AMR)

AF:

0.00

AC:

AN:

35696

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25180

East Asian (EAS)

AF:

0.00

AC:

AN:

35738

South Asian (SAS)

AF:

0.00

AC:

AN:

79228

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49276

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5698

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1078962

Other (OTH)

AF:

0.0000172

AC:

AN:

58002

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151792

Hom.:

Cov.:

AF XY:

0.0000270

AC XY:

AN XY:

74094

show subpopulations

African (AFR)

AF:

0.0000485

AC:

AN:

41250

American (AMR)

AF:

0.00

AC:

AN:

15222

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10548

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68000

Other (OTH)

AF:

0.00

AC:

AN:

2080

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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:

0.000142

Hom.:

Bravo

AF:

0.0000680

ESP6500AA

AF:

0.000723

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000406

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

0.14

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.36

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0033

Eigen

Uncertain

0.31

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.0086

MetaRNN

Uncertain

0.53

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

PhyloP100

6.3

PrimateAI

Uncertain

0.60

PROVEAN

Benign

0.28

REVEL

Benign

0.14

Sift

Uncertain

0.013

Sift4G

Benign

0.10

Polyphen

0.83

Vest4

0.75

MVP

0.59

MPC

1.2

ClinPred

0.49

GERP RS

5.1

Varity_R

0.27

gMVP

0.56

Mutation Taster

=66/34

polymorphism

(source)

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

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over