chr6-24645739-T-G

Variant names:

• chr6-24645739-T-G
• rs2038135
• NM_014809.4:c.-109A>C

Variant summary

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

The NM_001350404.2(KIAA0319):​c.34A>C​(p.Thr12Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.702 in 151,554 control chromosomes in the GnomAD database, including 37,902 homozygotes. In-silico tool predicts a benign outcome for this variant. 5/5 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.70 (37812 hom., cov: 29)
  • Exomes 𝑓: 0.64 (90 hom.)
• Consequence: KIAA0319 NM_001350404.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.813
• Publications: 12 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.851 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001350404.2. 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.-109A>C		5_prime_UTR	Exon 1 of 21	NP_055624.2	Q5VV43-1
	KIAA0319	NM_001350404.2		c.34A>C	p.Thr12Pro	missense	Exon 1 of 20	NP_001337333.1
	KIAA0319	NM_001168375.2		c.-218A>C		5_prime_UTR	Exon 1 of 21	NP_001161847.1	Q5VV43-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIAA0319	ENST00000378214.8	TSL:1 MANE Select	c.-109A>C		5_prime_UTR	Exon 1 of 21	ENSP00000367459.3	Q5VV43-1
	KIAA0319	ENST00000537886.5	TSL:1	c.-109A>C		5_prime_UTR	Exon 1 of 19	ENSP00000439700.1	Q5VV43-4
	KIAA0319	ENST00000937457.1		c.-218A>C		5_prime_UTR	Exon 1 of 21	ENSP00000607516.1

Frequencies

GnomAD3 genomes AF: 0.702 AC: 106048 AN: 151022 Hom.: 37783 Cov.: 29

Gnomad AFR AF: 0.796

Gnomad AMI AF: 0.784

Gnomad AMR AF: 0.767

Gnomad ASJ AF: 0.621

Gnomad EAS AF: 0.872

Gnomad SAS AF: 0.697

Gnomad FIN AF: 0.537

Gnomad MID AF: 0.799

Gnomad NFE AF: 0.646

Gnomad OTH AF: 0.705

GnomAD4 exome AF: 0.641 AC: 264 AN: 412 Hom.: 90 Cov.: 0 AF XY: 0.645 AC XY: 160 AN XY: 248

African (AFR) AF: 0.400 AC: 4 AN: 10

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.786 AC: 11 AN: 14

East Asian (EAS) AF: 0.833 AC: 20 AN: 24

South Asian (SAS) AF: 0.500 AC: 2 AN: 4

European-Finnish (FIN) AF: 0.684 AC: 26 AN: 38

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.609 AC: 184 AN: 302

Other (OTH) AF: 0.850 AC: 17 AN: 20

GnomAD4 genome AF: 0.702 AC: 106129 AN: 151142 Hom.: 37812 Cov.: 29 AF XY: 0.699 AC XY: 51571 AN XY: 73812

African (AFR) AF: 0.795 AC: 32794 AN: 41228

American (AMR) AF: 0.767 AC: 11646 AN: 15182

Ashkenazi Jewish (ASJ) AF: 0.621 AC: 2144 AN: 3452

East Asian (EAS) AF: 0.872 AC: 4445 AN: 5096

South Asian (SAS) AF: 0.695 AC: 3322 AN: 4778

European-Finnish (FIN) AF: 0.537 AC: 5636 AN: 10488

Middle Eastern (MID) AF: 0.802 AC: 231 AN: 288

European-Non Finnish (NFE) AF: 0.646 AC: 43720 AN: 67638

Other (OTH) AF: 0.710 AC: 1490 AN: 2098

Alfa AF: 0.670 Hom.: 36809

Bravo AF: 0.724

Asia WGS AF: 0.790 AC: 2745 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.9
DANN	Benign	0.81
PhyloP100		-0.81
PromoterAI		-0.030	Neutral
Mutation Taster		=300/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs2038135; hg19: chr6-24645967;