Genetic Variant NM_007245.4:c.235C>A (chr16-28823494-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_007245.4(ATXN2L):c.235C>A(p.Pro79Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000813 in 1,229,938 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P79L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 8.1e-7 ( 0 hom. )

Consequence

ATXN2L
NM_007245.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.610

Publications

0 publications found

Variant links:

Genes affected

ATXN2L (HGNC:31326): (ataxin 2 like) This gene encodes an ataxin type 2 related protein of unknown function. This protein is a member of the spinocerebellar ataxia (SCAs) family, which is associated with a complex group of neurodegenerative disorders. Several alternatively spliced transcripts encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ATXN2L links:

ENSG00000275807 (HGNC:):

ENSG00000275807 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0950509).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007245.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ATXN2L	NM_007245.4	MANE Select	c.235C>A	p.Pro79Thr	missense	Exon 1 of 22	NP_009176.2
ATXN2L	NM_001387166.1		c.235C>A	p.Pro79Thr	missense	Exon 1 of 24	NP_001374095.1
ATXN2L	NM_001387167.1		c.235C>A	p.Pro79Thr	missense	Exon 1 of 24	NP_001374096.1	Q8WWM7-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ATXN2L	ENST00000336783.9	TSL:1 MANE Select	c.235C>A	p.Pro79Thr	missense	Exon 1 of 22	ENSP00000338718.4	Q8WWM7-1
ATXN2L	ENST00000395547.6	TSL:1	c.235C>A	p.Pro79Thr	missense	Exon 1 of 24	ENSP00000378917.2	Q8WWM7-3
ATXN2L	ENST00000564304.5	TSL:1	c.235C>A	p.Pro79Thr	missense	Exon 1 of 23	ENSP00000457613.1	H3BUF6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

8.13e-7

AC:

AN:

1229938

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

601910

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24566

American (AMR)

AF:

0.00

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19536

East Asian (EAS)

AF:

0.00

AC:

AN:

27382

South Asian (SAS)

AF:

0.00

AC:

AN:

57436

European-Finnish (FIN)

AF:

0.00

AC:

AN:

29380

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3512

European-Non Finnish (NFE)

AF:

9.97e-7

AC:

AN:

1002798

Other (OTH)

AF:

0.00

AC:

AN:

50048

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.65

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.026

Eigen

Benign

-0.63

Eigen_PC

Benign

-0.51

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.63

M_CAP

Uncertain

0.22

MetaRNN

Benign

0.095

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

-0.61

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-0.16

REVEL

Benign

0.035

Sift

Benign

0.11

Sift4G

Benign

0.29

Polyphen

0.48

Vest4

0.16

MutPred

0.11

Gain of glycosylation at P79 (P = 0.0426)

MVP

0.26

MPC

0.56

ClinPred

0.080

GERP RS

1.8

PromoterAI

0.061

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.040

gMVP

0.19

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over