chr6-24559010-T-C

Variant names:

• chr6-24559010-T-C
• rs150584710
• NM_014809.4:c.2734+3A>G

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Moderate BP6 BS2

The NM_014809.4(KIAA0319):​c.2734+3A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000375 in 1,608,892 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00033 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00038 (2 hom.)
• Consequence: KIAA0319 NM_014809.4 splice_region, intron
• Scores: Splicing: ADA: 0.03965
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.66
• Publications: 0 publications found

Genes affected

KIAA0319 (HGNC:21580): (KIAA0319) This gene encodes a transmembrane protein that contains a large extracellular domain with multiple polycystic kidney disease (PKD) domains. The encoded protein may play a role in the development of the cerebral cortex by regulating neuronal migration and cell adhesion. Single nucleotide polymorphisms in this gene are associated with dyslexia. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Nov 2011]

ACMG classification

Our verdict: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP6: Variant 6-24559010-T-C is Benign according to our data. Variant chr6-24559010-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3036021.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014809.4. 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
	KIAA0319	NM_014809.4	MANE Select	c.2734+3A>G		splice_region intron	N/A	NP_055624.2	Q5VV43-1
	KIAA0319	NM_001168375.2		c.2734+3A>G		splice_region intron	N/A	NP_001161847.1	Q5VV43-1
	KIAA0319	NM_001350403.2		c.2734+3A>G		splice_region intron	N/A	NP_001337332.1	Q5VV43-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIAA0319	ENST00000378214.8	TSL:1 MANE Select	c.2734+3A>G		splice_region intron	N/A	ENSP00000367459.3	Q5VV43-1
	KIAA0319	ENST00000537886.5	TSL:1	c.2734+3A>G		splice_region intron	N/A	ENSP00000439700.1	Q5VV43-4
	KIAA0319	ENST00000616673.4	TSL:1	c.967+3A>G		splice_region intron	N/A	ENSP00000483665.1	A0A087X0U9

Frequencies

GnomAD3 genomes AF: 0.000328 AC: 50 AN: 152258 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.0000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000617

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000411 AC: 100 AN: 243294 AF XY: 0.000511

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000328

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000167

Gnomad FIN exome AF: 0.000189

Gnomad NFE exome AF: 0.000473

Gnomad OTH exome AF: 0.000335

GnomAD4 exome AF: 0.000380 AC: 554 AN: 1456516 Hom.: 2 Cov.: 30 AF XY: 0.000417 AC XY: 302 AN XY: 723964

African (AFR) AF: 0.0000299 AC: 1 AN: 33428

American (AMR) AF: 0.000319 AC: 14 AN: 43920

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25952

East Asian (EAS) AF: 0.00 AC: 0 AN: 39650

South Asian (SAS) AF: 0.000823 AC: 70 AN: 85034

European-Finnish (FIN) AF: 0.000150 AC: 8 AN: 53192

Middle Eastern (MID) AF: 0.00302 AC: 16 AN: 5304

European-Non Finnish (NFE) AF: 0.000388 AC: 431 AN: 1109844

Other (OTH) AF: 0.000233 AC: 14 AN: 60192

GnomAD4 genome AF: 0.000328 AC: 50 AN: 152376 Hom.: 1 Cov.: 33 AF XY: 0.000228 AC XY: 17 AN XY: 74510

African (AFR) AF: 0.0000481 AC: 2 AN: 41590

American (AMR) AF: 0.0000653 AC: 1 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000385 AC: 2 AN: 5194

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10632

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000617 AC: 42 AN: 68036

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.000360 Hom.: 0

Bravo AF: 0.000351

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	KIAA0319-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	15
DANN	Benign	0.91
PhyloP100		1.7
Mutation Taster		=82/18	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.040
dbscSNV1_RF	Benign	0.22
SpliceAI score (max)		0.16		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: rs150584710; hg19: chr6-24559238;