Genetic Variant ATCAY:p.Thr32Met (chr19-3902504-C-T) – ACMG Classification: Uncertain_significance (0 pts)

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

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]

ATCAY links:

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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
ATCAY	NM_033064.5 link	c.95C>T	p.Thr32Met	missense_variant	Exon 3 of 13	ENST00000450849.7	NP_149053.1	Q86WG3-1A0A0S2Z5T8
ATCAY	XM_047439578.1 link	c.-293C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 2 of 12		XP_047295534.1
ATCAY	XM_047439578.1 link	c.-293C>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.95C>T	p.Thr32Met	missense_variant	Exon 3 of 13	1	NM_033064.5	ENSP00000390941.1	Q86WG3-1
ATCAY	ENST00000600960.1 link	c.95C>T	p.Thr32Met	missense_variant	Exon 2 of 13	5		ENSP00000470842.1	Q86WG3-3
ATCAY	ENST00000598136.5 link	c.95C>T	p.Thr32Met	missense_variant	Exon 4 of 5	4		ENSP00000471731.1	M0R197
ATCAY	ENST00000597739.1 link	n.166C>T		non_coding_transcript_exon_variant	Exon 4 of 14	2		ENSP00000472263.1	M0R225

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152062

Hom.:

Cov.:

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:

AN:

197198

Hom.:

AF XY:

0.0000283

AC XY:

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:

AN:

1427848

Hom.:

Cov.:

AF XY:

0.0000453

AC XY:

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:

AN:

152062

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

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.:

Bravo

AF:

0.0000264

ExAC

AF:

0.00000835

AC:

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.19

.;T;.

Eigen

Benign

0.060

Eigen_PC

Benign

-0.011

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.90

D;D;D

M_CAP

Benign

0.023

MetaRNN

Benign

0.19

T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.9

.;L;L

PrimateAI

Uncertain

0.49

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

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over