NM_014809.4:c.2756G>C

Variant names:

• chr6-24556708-C-G
• rs10946705
• NM_014809.4:c.2756G>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_014809.4(KIAA0319):​c.2756G>C​(p.Gly919Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000346 in 1,613,854 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00045 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00033 (4 hom.)
• Consequence: KIAA0319 NM_014809.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 1.69
• Publications: 8 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.009059578).
• BP6: Variant 6-24556708-C-G is Benign according to our data. Variant chr6-24556708-C-G is described in ClinVar as Benign. ClinVar VariationId is 707909.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 4 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.2756G>C	p.Gly919Ala	missense	Exon 18 of 21	NP_055624.2	Q5VV43-1
	KIAA0319	NM_001168375.2		c.2756G>C	p.Gly919Ala	missense	Exon 18 of 21	NP_001161847.1	Q5VV43-1
	KIAA0319	NM_001350403.2		c.2756G>C	p.Gly919Ala	missense	Exon 18 of 21	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.2756G>C	p.Gly919Ala	missense	Exon 18 of 21	ENSP00000367459.3	Q5VV43-1
	KIAA0319	ENST00000537886.5	TSL:1	c.2756G>C	p.Gly919Ala	missense	Exon 18 of 19	ENSP00000439700.1	Q5VV43-4
	KIAA0319	ENST00000616673.4	TSL:1	c.989G>C	p.Gly330Ala	missense	Exon 14 of 17	ENSP00000483665.1	A0A087X0U9

Frequencies

GnomAD3 genomes AF: 0.000453 AC: 69 AN: 152192 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0125

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.000956

GnomAD2 exomes AF: 0.00120 AC: 300 AN: 250928 AF XY: 0.00105

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0160

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.000327

GnomAD4 exome AF: 0.000335 AC: 489 AN: 1461544 Hom.: 4 Cov.: 30 AF XY: 0.000300 AC XY: 218 AN XY: 727078

African (AFR) AF: 0.0000597 AC: 2 AN: 33478

American (AMR) AF: 0.0000224 AC: 1 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00985 AC: 391 AN: 39690

South Asian (SAS) AF: 0.00 AC: 0 AN: 86210

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53282

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5754

European-Non Finnish (NFE) AF: 0.00000630 AC: 7 AN: 1111904

Other (OTH) AF: 0.00144 AC: 87 AN: 60382

GnomAD4 genome AF: 0.000453 AC: 69 AN: 152310 Hom.: 1 Cov.: 32 AF XY: 0.000550 AC XY: 41 AN XY: 74480

African (AFR) AF: 0.00 AC: 0 AN: 41564

American (AMR) AF: 0.00 AC: 0 AN: 15300

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

East Asian (EAS) AF: 0.0126 AC: 65 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68030

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.0000676 Hom.: 0

Bravo AF: 0.000631

ExAC AF: 0.000964 AC: 117

Asia WGS AF: 0.00751 AC: 26 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	KIAA0319-related disorder (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.20	T
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.93	D
MetaRNN	Benign	0.0091	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.9	M
PhyloP100		1.7
PrimateAI	Uncertain	0.52	T
PROVEAN	Uncertain	-4.3	D
REVEL	Benign	0.26
Sift	Uncertain	0.015	D
Sift4G	Uncertain	0.033	D
Polyphen		1.0	D
Vest4		0.50
MVP		0.53
MPC		0.54
ClinPred		0.18	T
GERP RS		4.0
Varity_R		0.37
gMVP		0.71
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs10946705; hg19: chr6-24556936;