10-24466694-T-G

Position:

• chr10-24466694-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001282770.2(KIAA1217):​c.-97T>G 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 0.0839 in 985,288 control chromosomes in the GnomAD database, including 3,881 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 0.077 (640 hom., cov: 32)
  • Exomes 𝑓: 0.085 (3241 hom.)
• Consequence: KIAA1217 NM_001282770.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0200

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.167 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIAA1217	NM_019590.5	c.847-6534T>G		intron_variant		ENST00000376454.8	NP_062536.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIAA1217	ENST00000376454.8	c.847-6534T>G		intron_variant		1	NM_019590.5	ENSP00000365637.3

Frequencies

GnomAD3 genomes AF: 0.0772 AC: 11746 AN: 152156 Hom.: 634 Cov.: 32

Gnomad AFR AF: 0.0169

Gnomad AMI AF: 0.0868

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.0426

Gnomad EAS AF: 0.177

Gnomad SAS AF: 0.0468

Gnomad FIN AF: 0.195

Gnomad MID AF: 0.00955

Gnomad NFE AF: 0.0854

Gnomad OTH AF: 0.0674

GnomAD4 exome AF: 0.0852 AC: 70946 AN: 833014 Hom.: 3241 Cov.: 30 AF XY: 0.0854 AC XY: 32859 AN XY: 384688

Gnomad4 AFR exome AF: 0.00887

Gnomad4 AMR exome AF: 0.116

Gnomad4 ASJ exome AF: 0.0435

Gnomad4 EAS exome AF: 0.177

Gnomad4 SAS exome AF: 0.0459

Gnomad4 FIN exome AF: 0.207

Gnomad4 NFE exome AF: 0.0877

Gnomad4 OTH exome AF: 0.0781

GnomAD4 genome AF: 0.0772 AC: 11755 AN: 152274 Hom.: 640 Cov.: 32 AF XY: 0.0822 AC XY: 6120 AN XY: 74446

Gnomad4 AFR AF: 0.0169

Gnomad4 AMR AF: 0.109

Gnomad4 ASJ AF: 0.0426

Gnomad4 EAS AF: 0.177

Gnomad4 SAS AF: 0.0465

Gnomad4 FIN AF: 0.195

Gnomad4 NFE AF: 0.0854

Gnomad4 OTH AF: 0.0662

Alfa AF: 0.0824 Hom.: 74

Bravo AF: 0.0697

Asia WGS AF: 0.0890 AC: 311 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	10
DANN	Benign	0.81

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs16924796; hg19: chr10-24755623;