NM_019590.5:c.354+55815C>T

Variant names:

• chr10-24275724-C-T
• rs11014002
• NM_019590.5:c.354+55815C>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+55815C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0663 in 531,600 control chromosomes in the GnomAD database, including 1,754 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 0.050 (325 hom., cov: 33)
  • Exomes 𝑓: 0.073 (1429 hom.)
• Consequence: KIAA1217 NM_019590.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0970
• Publications: 25 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.213 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019590.5. 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
	KIAA1217	NM_019590.5	MANE Select	c.354+55815C>T		intron	N/A	NP_062536.2
	MIR603	NR_030334.1		n.40C>T		non_coding_transcript_exon	Exon 1 of 1
	KIAA1217	NM_001282767.2		c.354+55815C>T		intron	N/A	NP_001269696.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIAA1217	ENST00000376454.8	TSL:1 MANE Select	c.354+55815C>T		intron	N/A	ENSP00000365637.3
	KIAA1217	ENST00000376452.7	TSL:1	c.354+55815C>T		intron	N/A	ENSP00000365635.3
	KIAA1217	ENST00000458595.5	TSL:1	c.354+55815C>T		intron	N/A	ENSP00000392625.1

Frequencies

GnomAD3 genomes AF: 0.0504 AC: 7664 AN: 152060 Hom.: 323 Cov.: 33

Gnomad AFR AF: 0.0128

Gnomad AMI AF: 0.00989

Gnomad AMR AF: 0.0438

Gnomad ASJ AF: 0.0496

Gnomad EAS AF: 0.223

Gnomad SAS AF: 0.138

Gnomad FIN AF: 0.0528

Gnomad MID AF: 0.0669

Gnomad NFE AF: 0.0554

Gnomad OTH AF: 0.0566

GnomAD2 exomes AF: 0.0727 AC: 17624 AN: 242328 AF XY: 0.0768

Gnomad AFR exome AF: 0.0110

Gnomad AMR exome AF: 0.0446

Gnomad ASJ exome AF: 0.0587

Gnomad EAS exome AF: 0.231

Gnomad FIN exome AF: 0.0493

Gnomad NFE exome AF: 0.0553

Gnomad OTH exome AF: 0.0543

GnomAD4 exome AF: 0.0727 AC: 27585 AN: 379420 Hom.: 1429 Cov.: 0 AF XY: 0.0789 AC XY: 17052 AN XY: 216056

African (AFR) AF: 0.0107 AC: 111 AN: 10420

American (AMR) AF: 0.0447 AC: 1611 AN: 36014

Ashkenazi Jewish (ASJ) AF: 0.0592 AC: 693 AN: 11700

East Asian (EAS) AF: 0.230 AC: 3000 AN: 13040

South Asian (SAS) AF: 0.132 AC: 8771 AN: 66400

European-Finnish (FIN) AF: 0.0479 AC: 1537 AN: 32082

Middle Eastern (MID) AF: 0.0597 AC: 156 AN: 2614

European-Non Finnish (NFE) AF: 0.0556 AC: 10606 AN: 190606

Other (OTH) AF: 0.0665 AC: 1100 AN: 16544

GnomAD4 genome AF: 0.0504 AC: 7665 AN: 152180 Hom.: 325 Cov.: 33 AF XY: 0.0533 AC XY: 3962 AN XY: 74392

African (AFR) AF: 0.0128 AC: 532 AN: 41544

American (AMR) AF: 0.0438 AC: 670 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0496 AC: 172 AN: 3468

East Asian (EAS) AF: 0.224 AC: 1154 AN: 5158

South Asian (SAS) AF: 0.138 AC: 664 AN: 4814

European-Finnish (FIN) AF: 0.0528 AC: 559 AN: 10592

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0554 AC: 3766 AN: 67996

Other (OTH) AF: 0.0560 AC: 118 AN: 2108

Alfa AF: 0.0516 Hom.: 448

Bravo AF: 0.0460

Asia WGS AF: 0.151 AC: 526 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.5
DANN	Benign	0.35
PhyloP100		-0.097
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: rs11014002; hg19: chr10-24564653; COSMIC: COSV64606474;