Genetic Variant NM_001382309.1:c.947G>A (chr17-44194360-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001382309.1(ATXN7L3):c.947G>A(p.Ser316Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000657 in 1,614,228 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000053 ( 0 hom. )

Consequence

ATXN7L3
NM_001382309.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.83

Publications

1 publications found

Variant links:

Genes affected

ATXN7L3 (HGNC:25416): (ataxin 7 like 3) Enables nuclear receptor coactivator activity. Involved in histone deubiquitination; histone monoubiquitination; and positive regulation of transcription, DNA-templated. Located in nucleus. Part of DUBm complex and SAGA complex. [provided by Alliance of Genome Resources, Apr 2022]

ATXN7L3 Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder
Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics

ATXN7L3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008564651).

BS2

High AC in GnomAd4 at 28 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001382309.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ATXN7L3	NM_001382309.1	MANE Select	c.947G>A	p.Ser316Asn	missense	Exon 13 of 13	NP_001369238.1	Q14CW9-1
ATXN7L3	NM_001382316.1		c.1004G>A	p.Ser335Asn	missense	Exon 13 of 13	NP_001369245.1
ATXN7L3	NM_001382308.1		c.968G>A	p.Ser323Asn	missense	Exon 13 of 13	NP_001369237.1	Q14CW9-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ATXN7L3	ENST00000587097.6	TSL:5 MANE Select	c.947G>A	p.Ser316Asn	missense	Exon 13 of 13	ENSP00000465614.2	Q14CW9-1
ATXN7L3	ENST00000454077.6	TSL:1	c.968G>A	p.Ser323Asn	missense	Exon 12 of 12	ENSP00000397259.1	Q14CW9-2
ATXN7L3	ENST00000389384.8	TSL:1	c.947G>A	p.Ser316Asn	missense	Exon 12 of 12	ENSP00000374035.3	Q14CW9-1

Frequencies

GnomAD3 genomes

AF:

0.000184

AC:

AN:

152246

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.0186

Gnomad AMR

AF:

0.000392

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000764

AC:

AN:

248574

AF XY:

0.0000371

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000712

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.0000534

AC:

AN:

1461864

Hom.:

Cov.:

AF XY:

0.0000413

AC XY:

AN XY:

727236

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.000268

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53408

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000576

AC:

AN:

1112002

Other (OTH)

AF:

0.0000331

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.000184

AC:

AN:

152364

Hom.:

Cov.:

AF XY:

0.000174

AC XY:

AN XY:

74506

show subpopulations

African (AFR)

AF:

0.0000481

AC:

AN:

41582

American (AMR)

AF:

0.000392

AC:

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68036

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

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:

0.0000386

Hom.:

Bravo

AF:

0.000204

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000119

AC:

ExAC

AF:

0.0000661

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

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

0.11

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.48

CADD

Uncertain

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.039

Eigen

Benign

-0.50

Eigen_PC

Benign

-0.37

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.78

M_CAP

Benign

0.022

MetaRNN

Benign

0.0086

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.81

PhyloP100

3.8

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-0.56

REVEL

Benign

0.047

Sift

Uncertain

0.014

Sift4G

Pathogenic

0.0

Polyphen

0.047

Vest4

0.11

MVP

0.29

MPC

0.037

ClinPred

0.064

GERP RS

3.3

Varity_R

0.086

gMVP

0.16

Mutation Taster

=88/12

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over