Genetic Variant NM_024874.5:c.-80G>A (chr1-35557258-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_024874.5(KIAA0319L):c.-80G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0394 in 208,670 control chromosomes in the GnomAD database, including 464 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 0.049 ( 435 hom., cov: 33)

Exomes 𝑓: 0.013 ( 29 hom. )

Consequence

KIAA0319L
NM_024874.5 5_prime_UTR

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: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.31).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.23 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIAA0319L	NM_024874.5 link	c.-80G>A		5_prime_UTR_variant	Exon 1 of 21	ENST00000325722.8	NP_079150.3	Q8IZA0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIAA0319L	ENST00000325722.8 link	c.-80G>A		5_prime_UTR_variant	Exon 1 of 21	1	NM_024874.5	ENSP00000318406.3		Q8IZA0-1

Frequencies

GnomAD3 genomes

AF:

0.0493

AC:

7506

AN:

152180

Hom.:

434

Cov.:

show subpopulations

Gnomad AFR

AF:

0.106

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0770

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.242

Gnomad SAS

AF:

0.0284

Gnomad FIN

AF:

0.0241

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00287

Gnomad OTH

AF:

0.0458

GnomAD4 exome

AF:

0.0126

AC:

711

AN:

56372

Hom.:

Cov.:

AF XY:

0.0126

AC XY:

392

AN XY:

31114

show subpopulations

African (AFR)

AF:

0.0528

AC:

AN:

246

American (AMR)

AF:

0.0652

AC:

219

AN:

3360

Ashkenazi Jewish (ASJ)

AF:

0.00198

AC:

AN:

1010

East Asian (EAS)

AF:

0.169

AC:

AN:

528

South Asian (SAS)

AF:

0.0137

AC:

186

AN:

13562

European-Finnish (FIN)

AF:

0.0204

AC:

AN:

2740

Middle Eastern (MID)

AF:

0.0119

AC:

AN:

168

European-Non Finnish (NFE)

AF:

0.00322

AC:

103

AN:

31950

Other (OTH)

AF:

0.0146

AC:

AN:

2808

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

108

135

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0494

AC:

7519

AN:

152298

Hom.:

435

Cov.:

AF XY:

0.0516

AC XY:

3839

AN XY:

74464

show subpopulations

African (AFR)

AF:

0.106

AC:

4400

AN:

41564

American (AMR)

AF:

0.0774

AC:

1185

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00202

AC:

AN:

3472

East Asian (EAS)

AF:

0.241

AC:

1239

AN:

5146

South Asian (SAS)

AF:

0.0282

AC:

136

AN:

4826

European-Finnish (FIN)

AF:

0.0241

AC:

256

AN:

10626

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00287

AC:

195

AN:

68034

Other (OTH)

AF:

0.0458

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

351

702

1053

1404

1755

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00824

Hom.:

Bravo

AF:

0.0585

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.31

CADD

Benign

(source)

DANN

Benign

0.93

PhyloP100

2.5

PromoterAI

0.17

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

NM_024874.5:c.-80G>A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over