chr19-3885803-C-T

Variant names:

• chr19-3885803-C-T
• rs368213837
• NM_033064.5:c.36C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Moderate BP6 BP7 BS2

The NM_033064.5(ATCAY):​c.36C>T​(p.Asn12Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000646 in 1,552,240 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.00058 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00065 (3 hom.)
• Consequence: ATCAY NM_033064.5 synonymous
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:2
• Conservation: PhyloP100: -2.00
• Publications: 2 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BP6: Variant 19-3885803-C-T is Benign according to our data. Variant chr19-3885803-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 328984.
• BP7: Synonymous conserved (PhyloP=-2 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 3 AR gene

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.36C>T	p.Asn12Asn	synonymous	Exon 2 of 13	NP_149053.1	A0A0S2Z5T8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATCAY	ENST00000450849.7	TSL:1 MANE Select	c.36C>T	p.Asn12Asn	synonymous	Exon 2 of 13	ENSP00000390941.1	Q86WG3-1
	ATCAY	ENST00000861418.1		c.36C>T	p.Asn12Asn	synonymous	Exon 2 of 13	ENSP00000531477.1
	ATCAY	ENST00000600960.1	TSL:5	c.36C>T	p.Asn12Asn	synonymous	Exon 1 of 13	ENSP00000470842.1	Q86WG3-3

Frequencies

GnomAD3 genomes AF: 0.000585 AC: 89 AN: 152112 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00184

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000720

Gnomad OTH AF: 0.00335

GnomAD2 exomes AF: 0.000565 AC: 89 AN: 157478 AF XY: 0.000541

Gnomad AFR exome AF: 0.000122

Gnomad AMR exome AF: 0.00129

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000648

Gnomad NFE exome AF: 0.000691

Gnomad OTH exome AF: 0.00180

GnomAD4 exome AF: 0.000653 AC: 914 AN: 1400010 Hom.: 3 Cov.: 31 AF XY: 0.000599 AC XY: 414 AN XY: 690590

African (AFR) AF: 0.0000949 AC: 3 AN: 31600

American (AMR) AF: 0.00173 AC: 62 AN: 35790

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25192

East Asian (EAS) AF: 0.00 AC: 0 AN: 35762

South Asian (SAS) AF: 0.000278 AC: 22 AN: 79228

European-Finnish (FIN) AF: 0.000142 AC: 7 AN: 49390

Middle Eastern (MID) AF: 0.00131 AC: 7 AN: 5342

European-Non Finnish (NFE) AF: 0.000712 AC: 769 AN: 1079624

Other (OTH) AF: 0.000758 AC: 44 AN: 58082

GnomAD4 genome AF: 0.000585 AC: 89 AN: 152230 Hom.: 0 Cov.: 31 AF XY: 0.000672 AC XY: 50 AN XY: 74424

African (AFR) AF: 0.0000481 AC: 2 AN: 41554

American (AMR) AF: 0.00183 AC: 28 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4828

European-Finnish (FIN) AF: 0.0000943 AC: 1 AN: 10606

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

European-Non Finnish (NFE) AF: 0.000720 AC: 49 AN: 68012

Other (OTH) AF: 0.00331 AC: 7 AN: 2112

Alfa AF: 0.000469 Hom.: 0

Bravo AF: 0.000740

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	1	-	Cayman type cerebellar ataxia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	3.8
DANN	Benign	0.78
PhyloP100		-2.0
PromoterAI		-0.0087	Neutral

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: rs368213837; hg19: chr19-3885801; COSMIC: COSV56654126;