Genetic Variant ATXN7L3B:p.Pro78Ser (chr12-74538344-C-T) – 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_001136262.2(ATXN7L3B):c.232C>T(p.Pro78Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000058 in 1,551,990 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., 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: 2.92

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09330872).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATXN7L3B	NM_001136262.2 link	c.232C>T	p.Pro78Ser	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.232C>T	p.Pro78Ser	missense_variant	Exon 1 of 1	6	NM_001136262.2	ENSP00000430000.2		Q96GX2
ENSG00000257386	ENST00000550926.1 link	n.176G>A		non_coding_transcript_exon_variant	Exon 2 of 2	3

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

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

GnomAD3 exomes

AF:

0.00000646

AC:

AN:

154808

Hom.:

AF XY:

0.0000122

AC XY:

AN XY:

82040

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:

0.0000166

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000572

AC:

AN:

1399792

Hom.:

Cov.:

AF XY:

0.00000579

AC XY:

AN XY:

690420

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000649

Gnomad4 OTH exome

AF:

0.0000172

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152198

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 22, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.232C>T (p.P78S) alteration is located in exon 1 (coding exon 1) of the ATXN7L3B gene. This alteration results from a C to T substitution at nucleotide position 232, causing the proline (P) at amino acid position 78 to be replaced by a serine (S). 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

0.085

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.0093

Eigen

Benign

0.00018

Eigen_PC

Benign

0.081

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.70

M_CAP

Benign

0.010

MetaRNN

Benign

0.093

MetaSVM

Benign

-0.88

PrimateAI

Uncertain

0.60

PROVEAN

Benign

0.74

REVEL

Benign

0.034

Sift

Uncertain

0.014

Sift4G

Benign

0.22

Polyphen

0.27

Vest4

0.11

MutPred

0.19

Loss of catalytic residue at P78 (P = 0.0438);

MVP

0.085

MPC

0.37

ClinPred

0.63

GERP RS

4.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.6

Varity_R

0.090

gMVP

0.34

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