dbSNP rs532286720: ATXN1L:p.Thr109Pro (chr16-71850065-A-C) – 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_001137675.4(ATXN1L):c.325A>C(p.Thr109Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000193 in 1,551,616 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 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. T109A) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

ATXN1L
NM_001137675.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.37

Variant links:

Genes affected

ATXN1L (HGNC:33279): (ataxin 1 like) Predicted to enable DNA binding activity and RNA binding activity. Predicted to be involved in several processes, including learning or memory; regulation of transcription, DNA-templated; and social behavior. Predicted to act upstream of or within several processes, including lung alveolus development; negative regulation of transcription by RNA polymerase II; and positive regulation of hematopoietic stem cell proliferation. Located in nucleolus and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ATXN1L links:

IST1 (HGNC:28977): (IST1 factor associated with ESCRT-III) This gene encodes a protein with MIT-interacting motifs that interacts with components of endosomal sorting complexes required for transport (ESCRT). ESCRT functions in vesicle budding, such as that which occurs during membrane abscission in cytokinesis. There is a pseudogene for this gene on chromosome 19. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Aug 2012]

IST1 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=0.103542).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATXN1L	NM_001137675.4 link	c.325A>C	p.Thr109Pro	missense_variant	Exon 3 of 3	ENST00000427980.7	NP_001131147.1	P0C7T5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ATXN1L	ENST00000427980.7 link	c.325A>C	p.Thr109Pro	missense_variant	Exon 3 of 3	1	NM_001137675.4	ENSP00000415822.2	P0C7T5
ATXN1L	ENST00000683775.1 link	c.325A>C	p.Thr109Pro	missense_variant	Exon 3 of 3			ENSP00000507897.1	P0C7T5
IST1	ENST00000568581.5 link	c.-16+1994A>C		intron_variant	Intron 2 of 4	5		ENSP00000456200.1	H3BRE2
ATXN1L	ENST00000569119.1 link	n.119+1994A>C		intron_variant	Intron 2 of 3	5

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

152074

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000649

AC:

AN:

154122

Hom.:

AF XY:

0.0000122

AC XY:

AN XY:

81768

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000439

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:

1399424

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

690218

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000126

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152192

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

ExAC

AF:

0.0000422

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0023

Eigen

Benign

-0.11

Eigen_PC

Benign

0.026

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.67

M_CAP

Benign

0.015

MetaRNN

Benign

0.10

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.34

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.90

REVEL

Benign

0.18

Sift

Uncertain

0.013

Sift4G

Benign

0.098

Polyphen

0.61

Vest4

0.32

MutPred

0.31

Gain of disorder (P = 0.0284);

MVP

0.30

ClinPred

0.19

GERP RS

4.3

Varity_R

0.11

gMVP

0.55

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over