19-3885778-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_033064.5(ATCAY):​c.11C>T​(p.Thr4Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000709 in 1,551,382 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: 𝑓 0.000020 ( 0 hom., cov: 30)
Exomes 𝑓: 0.0000057 ( 0 hom. )

Consequence

ATCAY
NM_033064.5 missense

Scores

1
8
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.71
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]

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=0.24674943).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ATCAYNM_033064.5 linkc.11C>T p.Thr4Ile missense_variant Exon 2 of 13 ENST00000450849.7 NP_149053.1 Q86WG3-1A0A0S2Z5T8

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ATCAYENST00000450849.7 linkc.11C>T p.Thr4Ile missense_variant Exon 2 of 13 1 NM_033064.5 ENSP00000390941.1 Q86WG3-1

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152118
Hom.:
0
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.0000724
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000642
AC:
1
AN:
155842
Hom.:
0
AF XY:
0.0000121
AC XY:
1
AN XY:
82396
show subpopulations
Gnomad AFR exome
AF:
0.000123
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000572
AC:
8
AN:
1399264
Hom.:
0
Cov.:
31
AF XY:
0.00000580
AC XY:
4
AN XY:
690180
show subpopulations
Gnomad4 AFR exome
AF:
0.000190
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:
0.00
Gnomad4 OTH exome
AF:
0.0000345
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152118
Hom.:
0
Cov.:
30
AF XY:
0.0000135
AC XY:
1
AN XY:
74288
show subpopulations
Gnomad4 AFR
AF:
0.0000724
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000330
Hom.:
0
Bravo
AF:
0.0000416

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Inborn genetic diseases Uncertain:1
Jul 25, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.11C>T (p.T4I) alteration is located in exon 2 (coding exon 1) of the ATCAY gene. This alteration results from a C to T substitution at nucleotide position 11, causing the threonine (T) at amino acid position 4 to be replaced by an isoleucine (I). 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
Pathogenic
0.71
BayesDel_addAF
Benign
-0.18
T
BayesDel_noAF
Benign
-0.26
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.16
.;T;.
Eigen
Uncertain
0.29
Eigen_PC
Uncertain
0.25
FATHMM_MKL
Uncertain
0.85
D
LIST_S2
Uncertain
0.89
D;D;D
M_CAP
Benign
0.040
D
MetaRNN
Benign
0.25
T;T;T
MetaSVM
Benign
-0.84
T
MutationAssessor
Benign
1.6
.;L;L
PrimateAI
Uncertain
0.74
T
PROVEAN
Benign
-1.8
.;N;.
REVEL
Benign
0.097
Sift
Uncertain
0.0010
.;D;.
Sift4G
Uncertain
0.0060
D;D;D
Polyphen
0.96
.;D;.
Vest4
0.48, 0.41
MVP
0.76
MPC
0.69
ClinPred
0.28
T
GERP RS
4.4
Varity_R
0.16
gMVP
0.56

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs937126056; hg19: chr19-3885776; COSMIC: COSV56658760; API