19-3880660-A-G

Variant names:

• chr19-3880660-A-G
• rs140876148
• ENST00000598136.5:c.-140-250A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The ENST00000598136.5(ATCAY):​c.-140-250A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00376 in 152,058 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0038 (9 hom., cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ATCAY ENST00000598136.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.363
• 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 19-3880660-A-G is Benign according to our data. Variant chr19-3880660-A-G is described in ClinVar as Benign. ClinVar VariationId is 328981.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00376 (572/152058) while in subpopulation EAS AF = 0.0324 (166/5128). AF 95% confidence interval is 0.0284. There are 9 homozygotes in GnomAd4. There are 295 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 9 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000598136.5. 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.-390A>G		upstream_gene	N/A	NP_149053.1	A0A0S2Z5T8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATCAY	ENST00000598136.5	TSL:4	c.-140-250A>G		intron	N/A	ENSP00000471731.1	M0R197
	ATCAY	ENST00000450849.7	TSL:1 MANE Select	c.-390A>G		upstream_gene	N/A	ENSP00000390941.1	Q86WG3-1
	ATCAY	ENST00000861418.1		c.-390A>G		upstream_gene	N/A	ENSP00000531477.1

Frequencies

GnomAD3 genomes AF: 0.00376 AC: 571 AN: 151940 Hom.: 9 Cov.: 31

Gnomad AFR AF: 0.000967

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00859

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.0323

Gnomad SAS AF: 0.0110

Gnomad FIN AF: 0.00321

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00203

Gnomad OTH AF: 0.00384

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 78 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 52

African (AFR) AF: 0.00 AC: 0 AN: 4

American (AMR) AC: 0 AN: 0

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: 0.00 AC: 0 AN: 10

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 60

Other (OTH) AF: 0.00 AC: 0 AN: 4

GnomAD4 genome AF: 0.00376 AC: 572 AN: 152058 Hom.: 9 Cov.: 31 AF XY: 0.00397 AC XY: 295 AN XY: 74326

African (AFR) AF: 0.000964 AC: 40 AN: 41502

American (AMR) AF: 0.00852 AC: 130 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3468

East Asian (EAS) AF: 0.0324 AC: 166 AN: 5128

South Asian (SAS) AF: 0.0113 AC: 54 AN: 4798

European-Finnish (FIN) AF: 0.00321 AC: 34 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00203 AC: 138 AN: 67982

Other (OTH) AF: 0.00427 AC: 9 AN: 2106

Alfa AF: 0.00177 Hom.: 0

Bravo AF: 0.00434

Asia WGS AF: 0.0180 AC: 64 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Cayman type cerebellar ataxia (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	5.1
DANN	Benign	0.78
PhyloP100		0.36
PromoterAI		0.0030	Neutral
Mutation Taster		=300/0	polymorphism

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: rs140876148; hg19: chr19-3880658;