19-3902504-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.95C>T​(p.Thr32Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000386 in 1,579,910 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 (★). Synonymous variant affecting the same amino acid position (i.e. T32T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000041 ( 0 hom. )

Consequence

ATCAY
NM_033064.5 missense

Scores

5
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.24
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=0.18917239).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ATCAYNM_033064.5 linkc.95C>T p.Thr32Met missense_variant Exon 3 of 13 ENST00000450849.7 NP_149053.1 Q86WG3-1A0A0S2Z5T8
ATCAYXM_047439578.1 linkc.-293C>T 5_prime_UTR_premature_start_codon_gain_variant Exon 2 of 12 XP_047295534.1
ATCAYXM_047439578.1 linkc.-293C>T 5_prime_UTR_variant Exon 2 of 12 XP_047295534.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ATCAYENST00000450849.7 linkc.95C>T p.Thr32Met missense_variant Exon 3 of 13 1 NM_033064.5 ENSP00000390941.1 Q86WG3-1
ATCAYENST00000600960.1 linkc.95C>T p.Thr32Met missense_variant Exon 2 of 13 5 ENSP00000470842.1 Q86WG3-3
ATCAYENST00000598136.5 linkc.95C>T p.Thr32Met missense_variant Exon 4 of 5 4 ENSP00000471731.1 M0R197
ATCAYENST00000597739.1 linkn.166C>T non_coding_transcript_exon_variant Exon 4 of 14 2 ENSP00000472263.1 M0R225

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152062
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000483
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:
0.0000254
AC:
5
AN:
197198
Hom.:
0
AF XY:
0.0000283
AC XY:
3
AN XY:
106152
show subpopulations
Gnomad AFR exome
AF:
0.0000895
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000137
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000117
Gnomad OTH exome
AF:
0.000199
GnomAD4 exome
AF:
0.0000406
AC:
58
AN:
1427848
Hom.:
0
Cov.:
31
AF XY:
0.0000453
AC XY:
32
AN XY:
707146
show subpopulations
Gnomad4 AFR exome
AF:
0.0000610
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00100
Gnomad4 SAS exome
AF:
0.0000369
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000110
Gnomad4 OTH exome
AF:
0.0000339
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152062
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74284
show subpopulations
Gnomad4 AFR
AF:
0.0000483
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
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.0000264
ExAC
AF:
0.00000835
AC:
1

ClinVar

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

Submissions by phenotype

not provided Uncertain:1
Feb 01, 2022
CeGaT Center for Human Genetics Tuebingen
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.079
BayesDel_addAF
Benign
-0.19
T
BayesDel_noAF
Benign
-0.51
CADD
Benign
22
DANN
Uncertain
1.0
DEOGEN2
Benign
0.19
.;T;.
Eigen
Benign
0.060
Eigen_PC
Benign
-0.011
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Uncertain
0.90
D;D;D
M_CAP
Benign
0.023
T
MetaRNN
Benign
0.19
T;T;T
MetaSVM
Benign
-0.95
T
MutationAssessor
Benign
1.9
.;L;L
PrimateAI
Uncertain
0.49
T
PROVEAN
Benign
-1.4
.;N;.
REVEL
Benign
0.029
Sift
Benign
0.089
.;T;.
Sift4G
Uncertain
0.029
D;T;T
Polyphen
0.96
.;D;.
Vest4
0.51, 0.50
MVP
0.80
MPC
0.82
ClinPred
0.79
D
GERP RS
3.3
Varity_R
0.029
gMVP
0.25

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.14
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: rs769474716; hg19: chr19-3902502; API