19-3885803-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6BP7BS2

The NM_033064.5(ATCAY):​c.36C>T​(p.Asn12Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000646 in 1,552,240 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00058 ( 0 hom., cov: 31)
Exomes 𝑓: 0.00065 ( 3 hom. )

Consequence

ATCAY
NM_033064.5 synonymous

Scores

2

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2

Conservation

PhyloP100: -2.00
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 Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.32).
BP6
Variant 19-3885803-C-T is Benign according to our data. Variant chr19-3885803-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 328984.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=1}. Variant chr19-3885803-C-T is described in Lovd as [Likely_benign].
BP7
Synonymous conserved (PhyloP=-2 with no splicing effect.
BS2
High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ATCAYNM_033064.5 linkc.36C>T p.Asn12Asn synonymous_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.36C>T p.Asn12Asn synonymous_variant Exon 2 of 13 1 NM_033064.5 ENSP00000390941.1 Q86WG3-1

Frequencies

GnomAD3 genomes
AF:
0.000585
AC:
89
AN:
152112
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00184
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.0000943
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000720
Gnomad OTH
AF:
0.00335
GnomAD3 exomes
AF:
0.000565
AC:
89
AN:
157478
Hom.:
0
AF XY:
0.000541
AC XY:
45
AN XY:
83254
show subpopulations
Gnomad AFR exome
AF:
0.000122
Gnomad AMR exome
AF:
0.00129
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000175
Gnomad FIN exome
AF:
0.0000648
Gnomad NFE exome
AF:
0.000691
Gnomad OTH exome
AF:
0.00180
GnomAD4 exome
AF:
0.000653
AC:
914
AN:
1400010
Hom.:
3
Cov.:
31
AF XY:
0.000599
AC XY:
414
AN XY:
690590
show subpopulations
Gnomad4 AFR exome
AF:
0.0000949
Gnomad4 AMR exome
AF:
0.00173
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000278
Gnomad4 FIN exome
AF:
0.000142
Gnomad4 NFE exome
AF:
0.000712
Gnomad4 OTH exome
AF:
0.000758
GnomAD4 genome
AF:
0.000585
AC:
89
AN:
152230
Hom.:
0
Cov.:
31
AF XY:
0.000672
AC XY:
50
AN XY:
74424
show subpopulations
Gnomad4 AFR
AF:
0.0000481
Gnomad4 AMR
AF:
0.00183
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000414
Gnomad4 FIN
AF:
0.0000943
Gnomad4 NFE
AF:
0.000720
Gnomad4 OTH
AF:
0.00331
Alfa
AF:
0.000469
Hom.:
0
Bravo
AF:
0.000740

ClinVar

Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:2
Revision: criteria provided, conflicting classifications
LINK: link

Submissions by phenotype

not provided Benign:2
Dec 31, 2019
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Mar 01, 2024
CeGaT Center for Human Genetics Tuebingen
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

ATCAY: BP4, BP7 -

Cayman type cerebellar ataxia Uncertain:1
Jan 13, 2018
Illumina Laboratory Services, Illumina
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.32
CADD
Benign
3.8
DANN
Benign
0.78

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

LitVar

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

Other links and lift over

dbSNP: rs368213837; hg19: chr19-3885801; COSMIC: COSV56654126; API