rs10412199

chr19-3927773-G-Achr19-3927773-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_033064.5(ATCAY):c.*3181G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.389 in 152,180 control chromosomes in the GnomAD database, including 12,023 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.39 (12010 hom., cov: 32)
  • Exomes 𝑓: 0.52 (13 hom.)
• Consequence: ATCAY NM_033064.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.64

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant 19-3927773-G-A is Benign according to our data. Variant chr19-3927773-G-A is described in ClinVar as [Benign]. Clinvar id is 329202.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.598 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATCAY	NM_033064.5	c.*3181G>A		3_prime_UTR_variant	13/13	ENST00000450849.7
ATCAY	XM_047439578.1	c.*3181G>A		3_prime_UTR_variant	12/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATCAY	ENST00000450849.7	c.*3181G>A		3_prime_UTR_variant	13/13	1	NM_033064.5	P1

Frequencies

GnomAD3 genomes AF: 0.389 AC: 59088 AN: 151958 Hom.: 11991 Cov.: 32

Gnomad AFR AF: 0.397

Gnomad AMI AF: 0.341

Gnomad AMR AF: 0.494

Gnomad ASJ AF: 0.391

Gnomad EAS AF: 0.569

Gnomad SAS AF: 0.616

Gnomad FIN AF: 0.335

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.338

Gnomad OTH AF: 0.409

GnomAD4 exome AF: 0.519 AC: 54 AN: 104 Hom.: 13 Cov.: 0 AF XY: 0.487 AC XY: 39 AN XY: 80

Gnomad4 AFR exome AF: 0.250

Gnomad4 AMR exome AF: 0.500

Gnomad4 FIN exome AF: 0.750

Gnomad4 NFE exome AF: 0.533

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.389 AC: 59141 AN: 152076 Hom.: 12010 Cov.: 32 AF XY: 0.397 AC XY: 29483 AN XY: 74348

Gnomad4 AFR AF: 0.397

Gnomad4 AMR AF: 0.495

Gnomad4 ASJ AF: 0.391

Gnomad4 EAS AF: 0.568

Gnomad4 SAS AF: 0.616

Gnomad4 FIN AF: 0.335

Gnomad4 NFE AF: 0.338

Gnomad4 OTH AF: 0.406

Alfa AF: 0.361 Hom.: 15621

Bravo AF: 0.398

Asia WGS AF: 0.602 AC: 2088 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Cayman type cerebellar ataxia Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	0.12
Dann	Benign	0.53

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

Other links and lift over

dbSNP: rs10412199; hg19: chr19-3927771;