chr19-45205630-T-C

Position:

• chr19-45205630-T-C

Variant summary

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

The ENST00000587566.5(MARK4):​c.-276-53359T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 151,972 control chromosomes in the GnomAD database, including 6,417 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 (6417 hom., cov: 32)
• Consequence: MARK4 ENST00000587566.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13

Genes affected

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]

BLOC1S3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.413 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BLOC1S3	XR_007066811.1	n.1526+3123T>C		intron_variant
BLOC1S3	XR_007066812.1	n.1526+3123T>C		intron_variant
BLOC1S3	XR_007066813.1	n.1498+3123T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MARK4	ENST00000587566.5	c.-276-53359T>C		intron_variant		5		ENSP00000465414.1
BLOC1S3	ENST00000591569.1	n.282+3123T>C		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40307 AN: 151854 Hom.: 6393 Cov.: 32

Gnomad AFR AF: 0.418

Gnomad AMI AF: 0.291

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.0738

Gnomad EAS AF: 0.364

Gnomad SAS AF: 0.323

Gnomad FIN AF: 0.251

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.166

Gnomad OTH AF: 0.214

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

GnomAD4 genome AF: 0.266 AC: 40388 AN: 151972 Hom.: 6417 Cov.: 32 AF XY: 0.272 AC XY: 20204 AN XY: 74266

Gnomad4 AFR AF: 0.418

Gnomad4 AMR AF: 0.303

Gnomad4 ASJ AF: 0.0738

Gnomad4 EAS AF: 0.365

Gnomad4 SAS AF: 0.323

Gnomad4 FIN AF: 0.251

Gnomad4 NFE AF: 0.167

Gnomad4 OTH AF: 0.222

Alfa AF: 0.171 Hom.: 1274

Bravo AF: 0.275

Asia WGS AF: 0.433 AC: 1504 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	1.8
DANN	Benign	0.56

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs597668; hg19: chr19-45708888;