19-3902506-G-A

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_033064.5(ATCAY):c.97G>A(p.Gly33Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000035 in 1,428,326 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G33E) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000035 ( 0 hom. )

Consequence

ATCAY
NM_033064.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.04

Publications

0 publications found

Variant links:

Genes affected

ATCAY (HGNC:779): (ATCAY kinesin light chain interacting caytaxin) This gene encodes a neuron-restricted protein that contains a CRAL-TRIO motif common to proteins that bind small lipophilic molecules. Mutations in this gene are associated with cerebellar ataxia, Cayman type. [provided by RefSeq, Jul 2008]

ATCAY Gene-Disease associations (from GenCC):

cerebellar ataxia
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
Cayman type cerebellar ataxia
Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet

ATCAY links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATCAY	NM_033064.5 link	c.97G>A	p.Gly33Arg	missense_variant	Exon 3 of 13	ENST00000450849.7	NP_149053.1	Q86WG3-1A0A0S2Z5T8
ATCAY	XM_047439578.1 link	c.-291G>A		5_prime_UTR_variant	Exon 2 of 12		XP_047295534.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ATCAY	ENST00000450849.7 link	c.97G>A	p.Gly33Arg	missense_variant	Exon 3 of 13	1	NM_033064.5	ENSP00000390941.1	Q86WG3-1
ATCAY	ENST00000600960.1 link	c.97G>A	p.Gly33Arg	missense_variant	Exon 2 of 13	5		ENSP00000470842.1	Q86WG3-3
ATCAY	ENST00000598136.5 link	c.97G>A	p.Gly33Arg	missense_variant	Exon 4 of 5	4		ENSP00000471731.1	M0R197
ATCAY	ENST00000597739.1 link	n.168G>A		non_coding_transcript_exon_variant	Exon 4 of 14	2		ENSP00000472263.1	M0R225

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000152

AC:

AN:

197554

AF XY:

0.0000188

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000350

AC:

AN:

1428326

Hom.:

Cov.:

AF XY:

0.00000565

AC XY:

AN XY:

707422

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32794

American (AMR)

AF:

0.00

AC:

AN:

39760

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25478

East Asian (EAS)

AF:

0.00

AC:

AN:

37970

South Asian (SAS)

AF:

0.0000615

AC:

AN:

81270

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50940

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5734

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1095282

Other (OTH)

AF:

0.00

AC:

AN:

59098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000250

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Jun 08, 2022

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.97G>A (p.G33R) alteration is located in exon 3 (coding exon 2) of the ATCAY gene. This alteration results from a G to A substitution at nucleotide position 97, causing the glycine (G) at amino acid position 33 to be replaced by an arginine (R). 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

0.19

BayesDel_addAF

Benign

-0.082

BayesDel_noAF

Benign

-0.36

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.50

.;T;.

Eigen

Uncertain

0.41

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.89

D;D;D

M_CAP

Benign

0.048

MetaRNN

Uncertain

0.57

D;D;D

MetaSVM

Benign

-0.46

MutationAssessor

Uncertain

2.0

.;M;M

PhyloP100

7.0

PrimateAI

Uncertain

0.51

PROVEAN

Uncertain

-3.9

.;D;.

REVEL

Benign

0.20

Sift

Uncertain

0.0060

.;D;.

Sift4G

Benign

0.083

T;D;D

Polyphen

0.99

.;D;.

Vest4

0.46, 0.45

MVP

0.88

MPC

1.3

ClinPred

0.80

GERP RS

4.3

Varity_R

0.20

gMVP

0.36

Mutation Taster

=92/8

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over