10-24275902-C-T

Variant names:

• chr10-24275902-C-T
• rs10764458
• NM_019590.5:c.354+55993C>T

Variant summary

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

The NM_019590.5(KIAA1217):​c.354+55993C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.914 in 428,112 control chromosomes in the GnomAD database, including 180,223 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 0.94 (67506 hom., cov: 32)
  • Exomes 𝑓: 0.90 (112717 hom.)
• Consequence: KIAA1217 NM_019590.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.403
• Publications: 5 publications found

Genes affected

KIAA1217 (HGNC:25428): (KIAA1217) Predicted to be involved in embryonic skeletal system development. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

MIR603 (HGNC:32859): (microRNA 603) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.967 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIAA1217	NM_019590.5	c.354+55993C>T		intron_variant	Intron 2 of 20	ENST00000376454.8	NP_062536.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIAA1217	ENST00000376454.8	c.354+55993C>T		intron_variant	Intron 2 of 20	1	NM_019590.5	ENSP00000365637.3

Frequencies

GnomAD3 genomes AF: 0.940 AC: 143025 AN: 152122 Hom.: 67472 Cov.: 32

Gnomad AFR AF: 0.975

Gnomad AMI AF: 0.888

Gnomad AMR AF: 0.942

Gnomad ASJ AF: 0.923

Gnomad EAS AF: 0.782

Gnomad SAS AF: 0.724

Gnomad FIN AF: 0.973

Gnomad MID AF: 0.953

Gnomad NFE AF: 0.943

Gnomad OTH AF: 0.925

GnomAD4 exome AF: 0.899 AC: 248130 AN: 275872 Hom.: 112717 AF XY: 0.883 AC XY: 136641 AN XY: 154666

African (AFR) AF: 0.974 AC: 6525 AN: 6698

American (AMR) AF: 0.941 AC: 17242 AN: 18326

Ashkenazi Jewish (ASJ) AF: 0.920 AC: 4854 AN: 5274

East Asian (EAS) AF: 0.787 AC: 8725 AN: 11090

South Asian (SAS) AF: 0.735 AC: 35962 AN: 48916

European-Finnish (FIN) AF: 0.975 AC: 25735 AN: 26402

Middle Eastern (MID) AF: 0.909 AC: 2144 AN: 2358

European-Non Finnish (NFE) AF: 0.939 AC: 135881 AN: 144690

Other (OTH) AF: 0.913 AC: 11062 AN: 12118

GnomAD4 genome AF: 0.940 AC: 143110 AN: 152240 Hom.: 67506 Cov.: 32 AF XY: 0.938 AC XY: 69788 AN XY: 74426

African (AFR) AF: 0.975 AC: 40509 AN: 41554

American (AMR) AF: 0.941 AC: 14388 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.923 AC: 3206 AN: 3472

East Asian (EAS) AF: 0.782 AC: 4014 AN: 5130

South Asian (SAS) AF: 0.724 AC: 3488 AN: 4820

European-Finnish (FIN) AF: 0.973 AC: 10336 AN: 10620

Middle Eastern (MID) AF: 0.946 AC: 278 AN: 294

European-Non Finnish (NFE) AF: 0.943 AC: 64142 AN: 68032

Other (OTH) AF: 0.918 AC: 1939 AN: 2112

Alfa AF: 0.945 Hom.: 13779

Bravo AF: 0.942

Asia WGS AF: 0.756 AC: 2633 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.91
DANN	Benign	0.32
PhyloP100		-0.40
Mutation Taster		=100/0	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: rs10764458; hg19: chr10-24564831;