10-24524398-A-G

Variant names:

• chr10-24524398-A-G
• rs2297328
• NM_019590.5:c.2532A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_019590.5(KIAA1217):​c.2532A>G​(p.Thr844Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0614 in 1,614,102 control chromosomes in the GnomAD database, including 5,210 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 0.12 (1698 hom., cov: 33)
  • Exomes 𝑓: 0.056 (3512 hom.)
• Consequence: KIAA1217 NM_019590.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.34
• Publications: 7 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]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP7: Synonymous conserved (PhyloP=-4.34 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.263 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIAA1217	NM_019590.5	MANE Select	c.2532A>G	p.Thr844Thr	synonymous	Exon 13 of 21	NP_062536.2
	KIAA1217	NM_001282767.2		c.2427A>G	p.Thr809Thr	synonymous	Exon 12 of 19	NP_001269696.1
	KIAA1217	NM_001282768.2		c.2427A>G	p.Thr809Thr	synonymous	Exon 12 of 18	NP_001269697.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIAA1217	ENST00000376454.8	TSL:1 MANE Select	c.2532A>G	p.Thr844Thr	synonymous	Exon 13 of 21	ENSP00000365637.3
	KIAA1217	ENST00000376451.4	TSL:1	c.1581A>G	p.Thr527Thr	synonymous	Exon 8 of 15	ENSP00000365634.2
	KIAA1217	ENST00000376452.7	TSL:1	c.2427A>G	p.Thr809Thr	synonymous	Exon 12 of 19	ENSP00000365635.3

Frequencies

GnomAD3 genomes AF: 0.115 AC: 17462 AN: 152142 Hom.: 1679 Cov.: 33

Gnomad AFR AF: 0.267

Gnomad AMI AF: 0.0450

Gnomad AMR AF: 0.0914

Gnomad ASJ AF: 0.0311

Gnomad EAS AF: 0.149

Gnomad SAS AF: 0.0923

Gnomad FIN AF: 0.0594

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0414

Gnomad OTH AF: 0.0914

GnomAD2 exomes AF: 0.0810 AC: 20346 AN: 251338 AF XY: 0.0758

Gnomad AFR exome AF: 0.277

Gnomad AMR exome AF: 0.102

Gnomad ASJ exome AF: 0.0337

Gnomad EAS exome AF: 0.158

Gnomad FIN exome AF: 0.0558

Gnomad NFE exome AF: 0.0426

Gnomad OTH exome AF: 0.0593

GnomAD4 exome AF: 0.0558 AC: 81539 AN: 1461842 Hom.: 3512 Cov.: 31 AF XY: 0.0554 AC XY: 40263 AN XY: 727222

African (AFR) AF: 0.273 AC: 9139 AN: 33476

American (AMR) AF: 0.0972 AC: 4347 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.0342 AC: 893 AN: 26134

East Asian (EAS) AF: 0.135 AC: 5349 AN: 39696

South Asian (SAS) AF: 0.0867 AC: 7478 AN: 86250

European-Finnish (FIN) AF: 0.0551 AC: 2941 AN: 53410

Middle Eastern (MID) AF: 0.0506 AC: 292 AN: 5768

European-Non Finnish (NFE) AF: 0.0424 AC: 47164 AN: 1111994

Other (OTH) AF: 0.0652 AC: 3936 AN: 60396

GnomAD4 genome AF: 0.115 AC: 17512 AN: 152260 Hom.: 1698 Cov.: 33 AF XY: 0.116 AC XY: 8628 AN XY: 74474

African (AFR) AF: 0.267 AC: 11098 AN: 41520

American (AMR) AF: 0.0912 AC: 1395 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0311 AC: 108 AN: 3472

East Asian (EAS) AF: 0.149 AC: 770 AN: 5174

South Asian (SAS) AF: 0.0913 AC: 441 AN: 4830

European-Finnish (FIN) AF: 0.0594 AC: 631 AN: 10626

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0414 AC: 2817 AN: 68020

Other (OTH) AF: 0.0919 AC: 194 AN: 2112

Alfa AF: 0.0665 Hom.: 1350

Bravo AF: 0.125

Asia WGS AF: 0.128 AC: 446 AN: 3478

EpiCase AF: 0.0405

EpiControl AF: 0.0387

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.0030
DANN	Benign	0.26
PhyloP100		-4.3
Mutation Taster		=99/1	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: rs2297328; hg19: chr10-24813327; COSMIC: COSV56813717;