rs17356664

Variant names:

• chr19-45237513-C-T
• rs17356664
• NM_001382422.1:c.523+1010G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001382422.1(EXOC3L2):​c.523+1010G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 151,852 control chromosomes in the GnomAD database, including 6,021 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.27 (6021 hom., cov: 31)
• Consequence: EXOC3L2 NM_001382422.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.56
• Publications: 29 publications found

Genes affected

EXOC3L2 (HGNC:30162): (exocyst complex component 3 like 2) The protein encoded by this gene is upregulated by vascular endothelial growth factor A and interacts with exocyst complex component 4. The encoded protein may be part of an exocyst complex that plays a role in cell membrane dynamics. Mutations in this gene may be associated with Alzheimer's disease. [provided by RefSeq, May 2017]

MARK4 (HGNC:13538): (microtubule affinity regulating kinase 4) This gene encodes a member of the microtubule affinity-regulating kinase family. These protein kinases phosphorylate microtubule-associated proteins and regulate the transition between stable and dynamic microtubules. The encoded protein is associated with the centrosome throughout mitosis and may be involved in cell cycle control. Expression of this gene is a potential marker for cancer, and the encoded protein may also play a role in Alzheimer's disease. Pseudogenes of this gene are located on both the short and long arm of chromosome 3. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2010]

MARK4 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.05).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.359 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001382422.1. 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
	EXOC3L2	NM_001382422.1	MANE Select	c.523+1010G>A		intron	N/A	NP_001369351.1	Q2M3D2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EXOC3L2	ENST00000413988.3	TSL:5 MANE Select	c.523+1010G>A		intron	N/A	ENSP00000400713.2	Q2M3D2
	EXOC3L2	ENST00000857198.1		c.523+1010G>A		intron	N/A	ENSP00000527257.1
	EXOC3L2	ENST00000952151.1		c.523+1010G>A		intron	N/A	ENSP00000622210.1

Frequencies

GnomAD3 genomes AF: 0.273 AC: 41451 AN: 151734 Hom.: 6010 Cov.: 31

Gnomad AFR AF: 0.256

Gnomad AMI AF: 0.274

Gnomad AMR AF: 0.203

Gnomad ASJ AF: 0.277

Gnomad EAS AF: 0.00954

Gnomad SAS AF: 0.373

Gnomad FIN AF: 0.329

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.304

Gnomad OTH AF: 0.259

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.273 AC: 41502 AN: 151852 Hom.: 6021 Cov.: 31 AF XY: 0.273 AC XY: 20275 AN XY: 74186

African (AFR) AF: 0.257 AC: 10649 AN: 41414

American (AMR) AF: 0.202 AC: 3085 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.277 AC: 961 AN: 3466

East Asian (EAS) AF: 0.00956 AC: 49 AN: 5126

South Asian (SAS) AF: 0.373 AC: 1795 AN: 4814

European-Finnish (FIN) AF: 0.329 AC: 3466 AN: 10548

Middle Eastern (MID) AF: 0.286 AC: 84 AN: 294

European-Non Finnish (NFE) AF: 0.304 AC: 20620 AN: 67920

Other (OTH) AF: 0.258 AC: 544 AN: 2110

Alfa AF: 0.288 Hom.: 16540

Bravo AF: 0.256

Asia WGS AF: 0.187 AC: 651 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.020
DANN	Benign	0.51
PhyloP100		-2.6

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs17356664; hg19: chr19-45740771;