1-35557258-C-T

Variant names:

• chr1-35557258-C-T
• rs28366021
• NM_024874.5:c.-80G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.50
• Publications: 6 publications found

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]

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

ACMG classification

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.

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>A		5_prime_UTR	Exon 1 of 21	NP_079150.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIAA0319L	ENST00000325722.8	TSL:1 MANE Select	c.-80G>A		5_prime_UTR	Exon 1 of 21	ENSP00000318406.3
	KIAA0319L	ENST00000461312.6	TSL:5	n.-80G>A		non_coding_transcript_exon	Exon 1 of 22	ENSP00000513058.1
	KIAA0319L	ENST00000473465.1	TSL:5	n.131G>A		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes AF: 0.0493 AC: 7506 AN: 152180 Hom.: 434 Cov.: 33

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.: 29 Cov.: 0 AF XY: 0.0126 AC XY: 392 AN XY: 31114

African (AFR) AF: 0.0528 AC: 13 AN: 246

American (AMR) AF: 0.0652 AC: 219 AN: 3360

Ashkenazi Jewish (ASJ) AF: 0.00198 AC: 2 AN: 1010

East Asian (EAS) AF: 0.169 AC: 89 AN: 528

South Asian (SAS) AF: 0.0137 AC: 186 AN: 13562

European-Finnish (FIN) AF: 0.0204 AC: 56 AN: 2740

Middle Eastern (MID) AF: 0.0119 AC: 2 AN: 168

European-Non Finnish (NFE) AF: 0.00322 AC: 103 AN: 31950

Other (OTH) AF: 0.0146 AC: 41 AN: 2808

GnomAD4 genome AF: 0.0494 AC: 7519 AN: 152298 Hom.: 435 Cov.: 33 AF XY: 0.0516 AC XY: 3839 AN XY: 74464

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: 7 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: 4 AN: 294

European-Non Finnish (NFE) AF: 0.00287 AC: 195 AN: 68034

Other (OTH) AF: 0.0458 AC: 97 AN: 2116

Alfa AF: 0.00824 Hom.: 3

Bravo AF: 0.0585

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	19
DANN	Benign	0.93
PhyloP100		2.5
PromoterAI		0.17	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs28366021; hg19: chr1-36022859;