dbSNP rs28366021: KIAA0319L:c.-80G>T (chr1-35557258-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_024874.5(KIAA0319L):c.-80G>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,192 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

KIAA0319L
NM_024874.5 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.50

Publications

6 publications found

Variant links:

Genes affected

KIAA0319L (HGNC:30071): (KIAA0319 like) Predicted to act upstream of or within several processes, including flagellated sperm motility; proacrosomal vesicle fusion; and receptor-mediated endocytosis of virus by host cell. Located in Golgi apparatus; cytoplasmic vesicle; and nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

KIAA0319L links:

NCDN (HGNC:17597): (neurochondrin) This gene encodes a leucine-rich cytoplasmic protein, which is highly similar to a mouse protein that negatively regulates Ca/calmodulin-dependent protein kinase II phosphorylation and may be essential for spatial learning processes. Several alternatively spliced transcript variants of this gene have been described. [provided by RefSeq, Jul 2008]

NCDN Gene-Disease associations (from GenCC):

neurodevelopmental disorder with infantile epileptic spasms
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
autosomal recessive non-syndromic intellectual disability
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

NCDN links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.29).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024874.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIAA0319L	NM_024874.5	MANE Select	c.-80G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 21	NP_079150.3
	KIAA0319L	NM_024874.5	MANE Select	c.-80G>T		5_prime_UTR	Exon 1 of 21	NP_079150.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
KIAA0319L	ENST00000325722.8	TSL:1 MANE Select	c.-80G>T	5_prime_UTR_premature_start_codon_gain	Exon 1 of 21	ENSP00000318406.3
KIAA0319L	ENST00000325722.8	TSL:1 MANE Select	c.-80G>T	5_prime_UTR	Exon 1 of 21	ENSP00000318406.3
KIAA0319L	ENST00000697002.1		c.-80G>T	5_prime_UTR_premature_start_codon_gain	Exon 1 of 19	ENSP00000513032.1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

56386

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

31124

African (AFR)

AF:

0.00

AC:

AN:

246

American (AMR)

AF:

0.00

AC:

AN:

3360

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1012

East Asian (EAS)

AF:

0.00

AC:

AN:

530

South Asian (SAS)

AF:

0.00

AC:

AN:

13564

European-Finnish (FIN)

AF:

0.00

AC:

AN:

2742

Middle Eastern (MID)

AF:

0.00

AC:

AN:

168

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

31956

Other (OTH)

AF:

0.00

AC:

AN:

2808

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152192

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41448

American (AMR)

AF:

0.00

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000194

AC:

AN:

5162

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68042

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.29

CADD

Benign

(source)

DANN

Benign

0.92

PhyloP100

2.5

PromoterAI

0.047

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over