19-45222848-T-C

Position:

• chr19-45222848-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001382422.1(EXOC3L2):​c.1719+1930A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0879 in 152,240 control chromosomes in the GnomAD database, including 800 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 0.088 (800 hom., cov: 31)
• Consequence: EXOC3L2 NM_001382422.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.907

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.16 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EXOC3L2	NM_001382422.1	c.1719+1930A>G		intron_variant		ENST00000413988.3	NP_001369351.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EXOC3L2	ENST00000413988.3	c.1719+1930A>G		intron_variant		5	NM_001382422.1	ENSP00000400713	P1
MARK4	ENST00000587566.5	c.-276-36141T>C		intron_variant		5		ENSP00000465414

Frequencies

GnomAD3 genomes AF: 0.0878 AC: 13362 AN: 152122 Hom.: 796 Cov.: 31

Gnomad AFR AF: 0.163

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.0489

Gnomad ASJ AF: 0.0202

Gnomad EAS AF: 0.107

Gnomad SAS AF: 0.0843

Gnomad FIN AF: 0.108

Gnomad MID AF: 0.0637

Gnomad NFE AF: 0.0499

Gnomad OTH AF: 0.0646

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

GnomAD4 genome AF: 0.0879 AC: 13387 AN: 152240 Hom.: 800 Cov.: 31 AF XY: 0.0890 AC XY: 6625 AN XY: 74424

Gnomad4 AFR AF: 0.163

Gnomad4 AMR AF: 0.0488

Gnomad4 ASJ AF: 0.0202

Gnomad4 EAS AF: 0.107

Gnomad4 SAS AF: 0.0837

Gnomad4 FIN AF: 0.108

Gnomad4 NFE AF: 0.0499

Gnomad4 OTH AF: 0.0705

Alfa AF: 0.0525 Hom.: 322

Bravo AF: 0.0860

Asia WGS AF: 0.120 AC: 418 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.6
DANN	Benign	0.46

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

Publications

LitVar

Other links and lift over

dbSNP: rs10422797; hg19: chr19-45726106;