19-3902528-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_033064.5(ATCAY):c.119C>T(p.Pro40Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000337 in 1,574,908 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000035 ( 0 hom. )

Consequence

ATCAY
NM_033064.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.99

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: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.076921254).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATCAY	NM_033064.5 link	c.119C>T	p.Pro40Leu	missense_variant	Exon 3 of 13	ENST00000450849.7	NP_149053.1	Q86WG3-1A0A0S2Z5T8
ATCAY	XM_047439578.1 link	c.-269C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 2 of 12		XP_047295534.1
ATCAY	XM_047439578.1 link	c.-269C>T		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.119C>T	p.Pro40Leu	missense_variant	Exon 3 of 13	1	NM_033064.5	ENSP00000390941.1	Q86WG3-1
ATCAY	ENST00000600960.1 link	c.119C>T	p.Pro40Leu	missense_variant	Exon 2 of 13	5		ENSP00000470842.1	Q86WG3-3
ATCAY	ENST00000598136.5 link	c.119C>T	p.Pro40Leu	missense_variant	Exon 4 of 5	4		ENSP00000471731.1	M0R197
ATCAY	ENST00000597739.1 link	n.190C>T		non_coding_transcript_exon_variant	Exon 4 of 14	2		ENSP00000472263.1	M0R225

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152096

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000482

AC:

AN:

186864

AF XY:

0.0000199

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000180

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000504

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000351

AC:

AN:

1422694

Hom.:

Cov.:

AF XY:

0.0000312

AC XY:

AN XY:

704006

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32642

American (AMR)

AF:

0.000257

AC:

AN:

38974

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25414

East Asian (EAS)

AF:

0.00

AC:

AN:

37582

South Asian (SAS)

AF:

0.0000371

AC:

AN:

80790

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50650

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5724

European-Non Finnish (NFE)

AF:

0.0000321

AC:

AN:

1092020

Other (OTH)

AF:

0.0000340

AC:

AN:

58898

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152214

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74406

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41542

American (AMR)

AF:

0.0000655

AC:

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68014

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000662

Hom.:

Bravo

AF:

0.0000491

ExAC

AF:

0.0000168

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

May 28, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.119C>T (p.P40L) alteration is located in exon 3 (coding exon 2) of the ATCAY gene. This alteration results from a C to T substitution at nucleotide position 119, causing the proline (P) at amino acid position 40 to be replaced by a leucine (L). 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

0.074

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Benign

0.78

DEOGEN2

Benign

0.15

.;T;.

Eigen

Benign

-0.57

Eigen_PC

Benign

-0.50

FATHMM_MKL

Uncertain

0.84

LIST_S2

Uncertain

0.90

D;D;D

M_CAP

Benign

0.011

MetaRNN

Benign

0.077

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.71

.;N;N

PhyloP100

3.0

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.78

.;N;.

REVEL

Benign

0.057

Sift

Benign

0.10

.;T;.

Sift4G

Benign

0.26

T;T;T

Polyphen

0.0

.;B;.

Vest4

0.19, 0.19

MVP

0.51

MPC

0.43

ClinPred

0.055

GERP RS

4.9

Varity_R

0.042

gMVP

0.20

Mutation Taster

=89/11

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

19-3902528-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over