Genetic Variant ATXN7L3B:p.Pro73Gln (chr12-74538330-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001136262.2(ATXN7L3B):c.218C>A(p.Pro73Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000571 in 1,400,314 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000057 ( 0 hom. )

Consequence

ATXN7L3B
NM_001136262.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.58

Variant links:

Genes affected

ATXN7L3B (HGNC:37931): (ataxin 7 like 3B) Involved in regulation of gene expression. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ATXN7L3B links:

ENSG00000257386 (HGNC:):

ENSG00000257386 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.30110043).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATXN7L3B	NM_001136262.2 link	c.218C>A	p.Pro73Gln	missense_variant	Exon 1 of 1	ENST00000519948.4	NP_001129734.1	Q96GX2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATXN7L3B	ENST00000519948.4 link	c.218C>A	p.Pro73Gln	missense_variant	Exon 1 of 1	6	NM_001136262.2	ENSP00000430000.2		Q96GX2
ENSG00000257386	ENST00000550926.1 link	n.190G>T		non_coding_transcript_exon_variant	Exon 2 of 2	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000643

AC:

AN:

155504

Hom.:

AF XY:

0.00

AC XY:

AN XY:

82360

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000165

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000571

AC:

AN:

1400314

Hom.:

Cov.:

AF XY:

0.00000724

AC XY:

AN XY:

690726

show subpopulations

Gnomad4 AFR exome

AF:

0.0000316

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000648

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000110

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 07, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.218C>A (p.P73Q) alteration is located in exon 1 (coding exon 1) of the ATXN7L3B gene. This alteration results from a C to A substitution at nucleotide position 218, causing the proline (P) at amino acid position 73 to be replaced by a glutamine (Q). 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

0.089

BayesDel_addAF

Uncertain

0.10

BayesDel_noAF

Benign

-0.090

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.090

Eigen

Uncertain

0.30

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.53

M_CAP

Benign

0.053

MetaRNN

Benign

0.30

MetaSVM

Benign

-0.52

PrimateAI

Uncertain

0.57

PROVEAN

Pathogenic

-5.1

REVEL

Benign

0.17

Sift

Pathogenic

0.0

Sift4G

Benign

0.092

Polyphen

0.99

Vest4

0.32

MutPred

0.36

Gain of sheet (P = 0.0085);

MVP

0.085

MPC

0.32

ClinPred

0.98

GERP RS

4.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.52

gMVP

0.26

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