rs10828663

Variant names:

• chr10-24524525-G-A
• rs10828663
• NM_019590.5:c.2659G>A

Variant summary

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

The NM_019590.5(KIAA1217):​c.2659G>A​(p.Ala887Thr) variant causes a missense change. The variant allele was found at a frequency of 0.254 in 1,613,792 control chromosomes in the GnomAD database, including 54,454 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.25 (4937 hom., cov: 32)
  • Exomes 𝑓: 0.25 (49517 hom.)
• Consequence: KIAA1217 NM_019590.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.47

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 (MetaRNN=0.007587403).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.273 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIAA1217	NM_019590.5	c.2659G>A	p.Ala887Thr	missense_variant	Exon 13 of 21	ENST00000376454.8	NP_062536.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIAA1217	ENST00000376454.8	c.2659G>A	p.Ala887Thr	missense_variant	Exon 13 of 21	1	NM_019590.5	ENSP00000365637.3

Frequencies

GnomAD3 genomes AF: 0.248 AC: 37681 AN: 151966 Hom.: 4939 Cov.: 32

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.410

Gnomad AMR AF: 0.242

Gnomad ASJ AF: 0.290

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.136

Gnomad FIN AF: 0.202

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.277

Gnomad OTH AF: 0.288

GnomAD3 exomes AF: 0.224 AC: 56132 AN: 250896 Hom.: 6816 AF XY: 0.226 AC XY: 30594 AN XY: 135646

Gnomad AFR exome AF: 0.231

Gnomad AMR exome AF: 0.170

Gnomad ASJ exome AF: 0.287

Gnomad EAS exome AF: 0.103

Gnomad SAS exome AF: 0.136

Gnomad FIN exome AF: 0.203

Gnomad NFE exome AF: 0.279

Gnomad OTH exome AF: 0.263

GnomAD4 exome AF: 0.255 AC: 372572 AN: 1461708 Hom.: 49517 Cov.: 36 AF XY: 0.252 AC XY: 183406 AN XY: 727158

Gnomad4 AFR exome AF: 0.237

Gnomad4 AMR exome AF: 0.181

Gnomad4 ASJ exome AF: 0.292

Gnomad4 EAS exome AF: 0.103

Gnomad4 SAS exome AF: 0.140

Gnomad4 FIN exome AF: 0.205

Gnomad4 NFE exome AF: 0.274

Gnomad4 OTH exome AF: 0.248

GnomAD4 genome AF: 0.248 AC: 37681 AN: 152084 Hom.: 4937 Cov.: 32 AF XY: 0.242 AC XY: 18017 AN XY: 74326

Gnomad4 AFR AF: 0.235

Gnomad4 AMR AF: 0.242

Gnomad4 ASJ AF: 0.290

Gnomad4 EAS AF: 0.112

Gnomad4 SAS AF: 0.135

Gnomad4 FIN AF: 0.202

Gnomad4 NFE AF: 0.277

Gnomad4 OTH AF: 0.284

Alfa AF: 0.274 Hom.: 14334

Bravo AF: 0.254

TwinsUK AF: 0.262 AC: 971

ALSPAC AF: 0.265 AC: 1022

ESP6500AA AF: 0.237 AC: 1043

ESP6500EA AF: 0.288 AC: 2478

ExAC AF: 0.226 AC: 27446

Asia WGS AF: 0.137 AC: 481 AN: 3478

EpiCase AF: 0.296

EpiControl AF: 0.297

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.011	.;T;.;.;.;T;.;.;.;.;.
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.47
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.73	.;T;T;T;T;T;T;T;T;T;T
MetaRNN	Benign	0.0076	T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	.;.;.;.;.;L;.;.;.;.;.
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.97	N;N;N;N;.;N;N;N;N;N;N
REVEL	Benign	0.087
Sift	Benign	0.18	T;T;T;.;.;T;T;T;T;T;T
Sift4G	Benign	0.22	T;T;T;T;T;T;T;T;T;T;T
Polyphen		0.086, 0.14, 0.17, 0.10, 0.44	.;.;B;.;.;B;.;B;B;B;B
Vest4		0.048
MPC		0.13
ClinPred		0.011	T
GERP RS		4.6
Varity_R		0.049
gMVP		0.30

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

Publications

LitVar

Other links and lift over

dbSNP: rs10828663; hg19: chr10-24813454; COSMIC: COSV56816626;