dbSNP rs769474716: ATCAY:p.Thr32Lys (chr19-3902504-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_033064.5(ATCAY):c.95C>A(p.Thr32Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000007 in 1,427,848 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T32M) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

ATCAY
NM_033064.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.24

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13945636).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATCAY	NM_033064.5 link	c.95C>A	p.Thr32Lys	missense_variant	Exon 3 of 13	ENST00000450849.7	NP_149053.1	Q86WG3-1A0A0S2Z5T8
ATCAY	XM_047439578.1 link	c.-293C>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.95C>A	p.Thr32Lys	missense_variant	Exon 3 of 13	1	NM_033064.5	ENSP00000390941.1	Q86WG3-1
ATCAY	ENST00000600960.1 link	c.95C>A	p.Thr32Lys	missense_variant	Exon 2 of 13	5		ENSP00000470842.1	Q86WG3-3
ATCAY	ENST00000598136.5 link	c.95C>A	p.Thr32Lys	missense_variant	Exon 4 of 5	4		ENSP00000471731.1	M0R197
ATCAY	ENST00000597739.1 link	n.166C>A		non_coding_transcript_exon_variant	Exon 4 of 14	2		ENSP00000472263.1	M0R225

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.00e-7

AC:

AN:

1427848

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

707146

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32788

American (AMR)

AF:

0.00

AC:

AN:

39684

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25464

East Asian (EAS)

AF:

0.00

AC:

AN:

37926

South Asian (SAS)

AF:

0.0000123

AC:

AN:

81258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50902

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5730

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1095026

Other (OTH)

AF:

0.00

AC:

AN:

59070

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

DANN

Benign

0.85

DEOGEN2

Benign

0.18

.;T;.

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.30

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.63

T;T;T

M_CAP

Benign

0.015

MetaRNN

Benign

0.14

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

.;L;L

PhyloP100

2.2

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-0.45

.;N;.

REVEL

Benign

0.049

Sift

Benign

0.78

.;T;.

Sift4G

Benign

0.27

T;T;T

Polyphen

0.28

.;B;.

Vest4

0.49, 0.47

MVP

0.66

MPC

0.55

ClinPred

0.25

GERP RS

3.3

Varity_R

0.043

gMVP

0.38

Mutation Taster

=92/8

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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

Computational scores

Splicing

Publications

Other links and lift over