rs769474716

Variant names:

• chr19-3902504-C-A
• rs769474716
• NM_033064.5:c.95C>A

Your query was ambiguous. Multiple possible variants found:

• chr19-3902504-C-A
• chr19-3902504-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.24
• Publications: 0 publications found

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

ACMG classification

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).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033064.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATCAY	NM_033064.5	MANE Select	c.95C>A	p.Thr32Lys	missense	Exon 3 of 13	NP_149053.1	A0A0S2Z5T8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATCAY	ENST00000450849.7	TSL:1 MANE Select	c.95C>A	p.Thr32Lys	missense	Exon 3 of 13	ENSP00000390941.1	Q86WG3-1
	ATCAY	ENST00000861418.1		c.95C>A	p.Thr32Lys	missense	Exon 3 of 13	ENSP00000531477.1
	ATCAY	ENST00000600960.1	TSL:5	c.95C>A	p.Thr32Lys	missense	Exon 2 of 13	ENSP00000470842.1	Q86WG3-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.00e-7 AC: 1 AN: 1427848 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 707146

African (AFR) AF: 0.00 AC: 0 AN: 32788

American (AMR) AF: 0.00 AC: 0 AN: 39684

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25464

East Asian (EAS) AF: 0.00 AC: 0 AN: 37926

South Asian (SAS) AF: 0.0000123 AC: 1 AN: 81258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50902

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5730

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1095026

Other (OTH) AF: 0.00 AC: 0 AN: 59070

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	16
DANN	Benign	0.85
DEOGEN2	Benign	0.18	T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.30
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L
PhyloP100		2.2
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-0.45	N
REVEL	Benign	0.049
Sift	Benign	0.78	T
Sift4G	Benign	0.27	T
Polyphen		0.28	B
Vest4		0.49
MVP		0.66
MPC		0.55
ClinPred		0.25	T
GERP RS		3.3
Varity_R		0.043
gMVP		0.38
Mutation Taster		=92/8	polymorphism

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

Other links and lift over

dbSNP: rs769474716; hg19: chr19-3902502;