rs10412199

Variant names:

• chr19-3927773-G-A
• rs10412199
• NM_033064.5:c.*3181G>A

Your query was ambiguous. Multiple possible variants found:

• chr19-3927773-G-A
• chr19-3927773-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.64
• Publications: 14 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: Benign. The variant received -20 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 VariationId is 329202.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
ATCAY	NM_033064.5	c.*3181G>A		3_prime_UTR_variant	Exon 13 of 13	ENST00000450849.7	NP_149053.1
ATCAY	XM_047439578.1	c.*3181G>A		3_prime_UTR_variant	Exon 12 of 12		XP_047295534.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATCAY	ENST00000450849.7	c.*3181G>A		3_prime_UTR_variant	Exon 13 of 13	1	NM_033064.5	ENSP00000390941.1

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

African (AFR) AF: 0.250 AC: 1 AN: 4

American (AMR) AF: 0.500 AC: 1 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.750 AC: 3 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.533 AC: 49 AN: 92

Other (OTH) AF: 0.00 AC: 0 AN: 2

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

African (AFR) AF: 0.397 AC: 16458 AN: 41492

American (AMR) AF: 0.495 AC: 7556 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.391 AC: 1357 AN: 3470

East Asian (EAS) AF: 0.568 AC: 2932 AN: 5160

South Asian (SAS) AF: 0.616 AC: 2973 AN: 4824

European-Finnish (FIN) AF: 0.335 AC: 3549 AN: 10586

Middle Eastern (MID) AF: 0.514 AC: 151 AN: 294

European-Non Finnish (NFE) AF: 0.338 AC: 22997 AN: 67972

Other (OTH) AF: 0.406 AC: 858 AN: 2114

Alfa AF: 0.364 Hom.: 28078

Bravo AF: 0.398

Asia WGS AF: 0.602 AC: 2088 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Cayman type cerebellar ataxia Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.12
DANN	Benign	0.53
PhyloP100		-2.6
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10412199; hg19: chr19-3927771;