Genetic Variant NM_033064.5:c.137-11T>C (chr19-3905423-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_033064.5(ATCAY):c.137-11T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00342 in 1,584,606 control chromosomes in the GnomAD database, including 153 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.019 ( 75 hom., cov: 31)

Exomes 𝑓: 0.0018 ( 78 hom. )

Consequence

ATCAY
NM_033064.5 intron

Scores

Splicing: ADA: 0.0001163

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.371

Publications

2 publications found

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 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

ATCAY links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 19-3905423-T-C is Benign according to our data. Variant chr19-3905423-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 329117.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.062 is higher than 0.05.

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.137-11T>C		intron	N/A	NP_149053.1	A0A0S2Z5T8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ATCAY	ENST00000450849.7	TSL:1 MANE Select	c.137-11T>C	intron	N/A	ENSP00000390941.1	Q86WG3-1
ATCAY	ENST00000861418.1		c.137-11T>C	intron	N/A	ENSP00000531477.1
ATCAY	ENST00000600960.1	TSL:5	c.137-11T>C	intron	N/A	ENSP00000470842.1	Q86WG3-3

Frequencies

GnomAD3 genomes

AF:

0.0189

AC:

2872

AN:

152080

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0640

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0104

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000265

Gnomad OTH

AF:

0.0201

GnomAD2 exomes

AF:

0.00476

AC:

1027

AN:

215718

AF XY:

0.00354

show subpopulations

Gnomad AFR exome

AF:

0.0690

Gnomad AMR exome

AF:

0.00344

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000146

Gnomad OTH exome

AF:

0.00130

GnomAD4 exome

AF:

0.00178

AC:

2544

AN:

1432408

Hom.:

Cov.:

AF XY:

0.00151

AC XY:

1072

AN XY:

709278

show subpopulations

African (AFR)

AF:

0.0650

AC:

2118

AN:

32584

American (AMR)

AF:

0.00386

AC:

151

AN:

39140

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25202

East Asian (EAS)

AF:

0.00

AC:

AN:

38860

South Asian (SAS)

AF:

0.000120

AC:

AN:

83146

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52486

Middle Eastern (MID)

AF:

0.000705

AC:

AN:

5670

European-Non Finnish (NFE)

AF:

0.0000265

AC:

AN:

1096058

Other (OTH)

AF:

0.00391

AC:

232

AN:

59262

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

118

236

353

471

589

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

136

204

272

340

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0189

AC:

2876

AN:

152198

Hom.:

Cov.:

AF XY:

0.0185

AC XY:

1380

AN XY:

74416

show subpopulations

African (AFR)

AF:

0.0640

AC:

2658

AN:

41538

American (AMR)

AF:

0.0104

AC:

158

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000265

AC:

AN:

68004

Other (OTH)

AF:

0.0199

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

138

275

413

550

688

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

140

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00932

Hom.:

Bravo

AF:

0.0218

Asia WGS

AF:

0.00404

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Cayman type cerebellar ataxia (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.58

(source)

DANN

Benign

0.41

PhyloP100

0.37

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00012

dbscSNV1_RF

Benign

0.026

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over