19-3902507-G-T

Variant names:

• chr19-3902507-G-T
• rs147031440
• NM_033064.5:c.98G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_033064.5(ATCAY):​c.98G>T​(p.Gly33Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000007 in 1,428,204 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. G33E) has been classified as Likely benign.

• 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: 4.03
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATCAY	NM_033064.5	c.98G>T	p.Gly33Val	missense_variant	Exon 3 of 13	ENST00000450849.7	NP_149053.1
ATCAY	XM_047439578.1	c.-290G>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
ATCAY	ENST00000450849.7	c.98G>T	p.Gly33Val	missense_variant	Exon 3 of 13	1	NM_033064.5	ENSP00000390941.1
ATCAY	ENST00000600960.1	c.98G>T	p.Gly33Val	missense_variant	Exon 2 of 13	5		ENSP00000470842.1
ATCAY	ENST00000598136.5	c.98G>T	p.Gly33Val	missense_variant	Exon 4 of 5	4		ENSP00000471731.1
ATCAY	ENST00000597739.1	n.169G>T		non_coding_transcript_exon_variant	Exon 4 of 14	2		ENSP00000472263.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.00e-7 AC: 1 AN: 1428204 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 707304

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 32794

American (AMR) AF: 0.00 AC: 0 AN: 39740

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25474

East Asian (EAS) AF: 0.00 AC: 0 AN: 37944

South Asian (SAS) AF: 0.00 AC: 0 AN: 81264

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50922

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5734

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1095250

Other (OTH) AF: 0.0000169 AC: 1 AN: 59082

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.065	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.53	.;D;.
Eigen	Uncertain	0.31
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.86	D;D;D
M_CAP	Benign	0.048	D
MetaRNN	Uncertain	0.59	D;D;D
MetaSVM	Benign	-0.66	T
MutationAssessor	Uncertain	2.0	.;M;M
PhyloP100		4.0
PrimateAI	Benign	0.46	T
PROVEAN	Pathogenic	-4.6	.;D;.
REVEL	Benign	0.15
Sift	Uncertain	0.0020	.;D;.
Sift4G	Uncertain	0.033	D;D;D
Polyphen		0.99	.;D;.
Vest4		0.54, 0.52
MVP		0.88
MPC		1.4
ClinPred		0.97	D
GERP RS		4.3
Varity_R		0.49
gMVP		0.41
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs147031440; hg19: chr19-3902505;